rs8177238

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001063.4(TF):c.887A>G(p.Asp296Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,614,242 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 40 hom. )

Consequence

TF
NM_001063.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.165

Publications

11 publications found

Variant links:

Genes affected

TF (HGNC:11740): (transferrin) This gene encodes a glycoprotein with an approximate molecular weight of 76.5 kDa. It is thought to have been created as a result of an ancient gene duplication event that led to generation of homologous C and N-terminal domains each of which binds one ion of ferric iron. The function of this protein is to transport iron from the intestine, reticuloendothelial system, and liver parenchymal cells to all proliferating cells in the body. This protein may also have a physiologic role as granulocyte/pollen-binding protein (GPBP) involved in the removal of certain organic matter and allergens from serum. [provided by RefSeq, Sep 2009]

TF Gene-Disease associations (from GenCC):

atransferrinemia
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp

TF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001835674).

BP6

Variant 3-133757785-A-G is Benign according to our data. Variant chr3-133757785-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 343441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0115 (1755/152370) while in subpopulation AFR AF = 0.0399 (1659/41580). AF 95% confidence interval is 0.0383. There are 38 homozygotes in GnomAd4. There are 802 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TF	NM_001063.4 link	c.887A>G	p.Asp296Gly	missense_variant	Exon 8 of 17	ENST00000402696.9	NP_001054.2	P02787Q06AH7A0PJA6
TF	NM_001354703.2 link	c.755A>G	p.Asp252Gly	missense_variant	Exon 14 of 23		NP_001341632.2
TF	NM_001354704.2 link	c.506A>G	p.Asp169Gly	missense_variant	Exon 7 of 16		NP_001341633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TF	ENST00000402696.9 link	c.887A>G	p.Asp296Gly	missense_variant	Exon 8 of 17	1	NM_001063.4	ENSP00000385834.3		P02787
TF	ENST00000485977.1 link	n.252A>G		non_coding_transcript_exon_variant	Exon 4 of 5	3		ENSP00000418716.1		F8WC57

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1744

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.00288

AC:

725

AN:

251428

AF XY:

0.00201

show subpopulations

Gnomad AFR exome

AF:

0.0401

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00120

AC:

1759

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000998

AC XY:

726

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0424

AC:

1418

AN:

33480

American (AMR)

AF:

0.00197

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

1111994

Other (OTH)

AF:

0.00270

AC:

163

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

174

261

348

435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0115

AC:

1755

AN:

152370

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

802

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.0399

AC:

1659

AN:

41580

American (AMR)

AF:

0.00451

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68036

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

172

258

344

430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00468

Hom.:

Bravo

AF:

0.0132

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0395

AC:

174

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00356

AC:

432

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 11, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Atransferrinemia

Benign:2

May 16, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.24

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

0.17

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

REVEL

Benign

0.042

Sift

Benign

0.36

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.041

MVP

0.23

MPC

0.45

ClinPred

0.0017

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.28

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over