Variant 1-149784224-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BS2_Supporting

The NM_000566.4(FCGR1A):c.274C>T(p.Arg92Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,611,110 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0039 ( 3 hom., cov: 27)

Exomes 𝑓: 0.0060 ( 42 hom. )

Consequence

FCGR1A
NM_000566.4 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.368

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:

LOC124904411 (HGNC:):

LOC124904411 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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5

Variant 1-149784224-C-T is Pathogenic according to our data. Variant chr1-149784224-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 14826.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR1A	NM_000566.4 linkuse as main transcript	c.274C>T	p.Arg92Ter	stop_gained	3/6	ENST00000369168.5	NP_000557.1
LOC124904411	XM_047438183.1 linkuse as main transcript	c.*577-964G>A		intron_variant			XP_047294139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR1A	ENST00000369168.5 linkuse as main transcript	c.274C>T	p.Arg92Ter	stop_gained	3/6	1	NM_000566.4	ENSP00000358165	P1	P12314-1
FCGR1A	ENST00000444948.5 linkuse as main transcript	c.31+1450C>T		intron_variant		2		ENSP00000394279
H2BC18	ENST00000545683.1 linkuse as main transcript	c.378-964G>A		intron_variant		2		ENSP00000445831		Q5QNW6-2
H2BC18	ENST00000420462.1 linkuse as main transcript	n.76-964G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00389

AC:

588

AN:

151310

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00440

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00651

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00410

AC:

1001

AN:

243930

Hom.:

AF XY:

0.00436

AC XY:

579

AN XY:

132946

show subpopulations

Gnomad AFR exome

AF:

0.00128

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.000303

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00475

Gnomad FIN exome

AF:

0.000515

Gnomad NFE exome

AF:

0.00630

Gnomad OTH exome

AF:

0.00439

GnomAD4 exome

AF:

0.00603

AC:

8796

AN:

1459686

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

4361

AN XY:

726152

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00441

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00709

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.00388

AC:

588

AN:

151424

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

262

AN XY:

73956

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00439

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.000379

Gnomad4 NFE

AF:

0.00652

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00469

Hom.:

Bravo

AF:

0.00407

ESP6500AA

AF:

0.00174

AC:

ESP6500EA

AF:

0.00493

AC:

ExAC

AF:

0.00401

AC:

478

EpiCase

AF:

0.00736

EpiControl

AF:

0.00762

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IGG receptor I, phagocytic, familial deficiency of

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 15, 1995

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Benign

0.090

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.052

MutationTaster

Benign

0.37

A;A;A;A

Vest4

0.51

GERP RS

3.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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