1-149791405-T-C

Position:

chr1-149791405-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000566.4(FCGR1A):c.1013T>C(p.Ile338Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,599,558 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 20 hom., cov: 26)

Exomes 𝑓: 0.0043 ( 306 hom. )

Consequence

FCGR1A
NM_000566.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.282

Variant links:

Genes affected

FCGR1A (HGNC:3613): (Fc gamma receptor Ia) This gene encodes a protein that plays an important role in the immune response. This protein is a high-affinity Fc-gamma receptor. The gene is one of three related gene family members located on chromosome 1. [provided by RefSeq, Jul 2008]

FCGR1A links:

ENSG00000233030 (HGNC:):

ENSG00000233030 links:

H2BC18 (HGNC:24700): (H2B clustered histone 18) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-dependent histone that is a member of the histone H2B family and is found in a histone cluster on chromosome 1. [provided by RefSeq, Aug 2015]

H2BC18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051913857).

BP6

Variant 1-149791405-T-C is Benign according to our data. Variant chr1-149791405-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1285171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-149791405-T-C is described in Lovd as [Likely_benign]. Variant chr1-149791405-T-C is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR1A	NM_000566.4 link	c.1013T>C	p.Ile338Thr	missense_variant	6/6	ENST00000369168.5	NP_000557.1	P12314-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR1A	ENST00000369168.5 link	c.1013T>C	p.Ile338Thr	missense_variant	6/6	1	NM_000566.4	ENSP00000358165.4		P12314-1

Frequencies

GnomAD3 genomes

AF:

0.00357

AC:

523

AN:

146444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000992

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00289

Gnomad ASJ

AF:

0.00879

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00504

Gnomad OTH

AF:

0.00351

GnomAD3 exomes

AF:

0.00418

AC:

1019

AN:

244050

Hom.:

102

AF XY:

0.00409

AC XY:

542

AN XY:

132610

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00820

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.000365

Gnomad FIN exome

AF:

0.00954

Gnomad NFE exome

AF:

0.00543

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00431

AC:

6264

AN:

1453008

Hom.:

306

Cov.:

AF XY:

0.00422

AC XY:

3051

AN XY:

722794

show subpopulations

Gnomad4 AFR exome

AF:

0.000908

Gnomad4 AMR exome

AF:

0.00220

Gnomad4 ASJ exome

AF:

0.00831

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000479

Gnomad4 FIN exome

AF:

0.00899

Gnomad4 NFE exome

AF:

0.00462

Gnomad4 OTH exome

AF:

0.00458

GnomAD4 genome

AF:

0.00357

AC:

523

AN:

146550

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

231

AN XY:

71638

show subpopulations

Gnomad4 AFR

AF:

0.000989

Gnomad4 AMR

AF:

0.00289

Gnomad4 ASJ

AF:

0.00879

Gnomad4 EAS

AF:

0.000200

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00661

Gnomad4 NFE

AF:

0.00504

Gnomad4 OTH

AF:

0.00347

Alfa

AF:

0.00448

Hom.:

Bravo

AF:

0.00333

ESP6500AA

AF:

0.000710

AC:

ESP6500EA

AF:

0.00554

AC:

ExAC

AF:

0.00433

AC:

510

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	FCGR1A: PP2, BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.17

DANN

Benign

0.66

DEOGEN2

Benign

0.051

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00035

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.6

PrimateAI

Benign

0.37

PROVEAN

Benign

0.96

REVEL

Benign

0.031

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.011

MVP

0.082

ClinPred

0.0014

GERP RS

-1.0

Varity_R

0.033

gMVP

0.028

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over