chr4-73438185-T-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001134.3(AFP):c.149T>A(p.Phe50Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,613,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

AFP
NM_001134.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0980

Publications

0 publications found

Variant links:

Genes affected

AFP (HGNC:317): (alpha fetoprotein) This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatocarcinoma and with teratoma, and has prognostic value for managing advanced gastric cancer. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. [provided by RefSeq, Oct 2019]

AFP Gene-Disease associations (from GenCC):

hereditary persistence of alpha-fetoprotein
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital deficiency in alpha-fetoprotein
Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

AFP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010208845).

BP6

Variant 4-73438185-T-A is Benign according to our data. Variant chr4-73438185-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3051185.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFP	NM_001134.3	MANE Select	c.149T>A	p.Phe50Tyr	missense	Exon 3 of 15	NP_001125.1	P02771
	AFP	NM_001354717.2		c.-184T>A		5_prime_UTR	Exon 3 of 16	NP_001341646.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFP	ENST00000395792.7	TSL:1 MANE Select	c.149T>A	p.Phe50Tyr	missense	Exon 3 of 15	ENSP00000379138.2	P02771
	AFP	ENST00000226359.2	TSL:5	c.149T>A	p.Phe50Tyr	missense	Exon 3 of 14	ENSP00000226359.2	J3KMX3

Frequencies

GnomAD3 genomes

AF:

0.000934

AC:

142

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000295

AC:

AN:

251202

AF XY:

0.000191

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000917

AC:

134

AN:

1461178

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

726892

show subpopulations

African (AFR)

AF:

0.00308

AC:

103

AN:

33450

American (AMR)

AF:

0.000380

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111500

Other (OTH)

AF:

0.000232

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000959

AC:

146

AN:

152210

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00327

AC:

136

AN:

41560

American (AMR)

AF:

0.000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000335

Hom.:

Bravo

AF:

0.00112

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000313

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

AFP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.58

M_CAP

Benign

0.0085

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

0.098

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.46

REVEL

Benign

0.13

Sift

Benign

0.055

Sift4G

Benign

0.075

Polyphen

0.59

Vest4

0.44

MVP

0.31

MPC

0.19

ClinPred

0.047

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.17

gMVP

0.20

Mutation Taster

=90/10

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over