rs74315310

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_000566.4(FCGR1A):c.274C>T(p.Arg92*) 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 Uncertain significance (★★). 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

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:2

Conservation

PhyloP100: 0.368

Publications

12 publications found

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:

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:

LOC124904411 (HGNC:):

LOC124904411 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

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 rank	MANE	Protein	UniProt
FCGR1A	NM_000566.4 link	c.274C>T	p.Arg92*	stop_gained	Exon 3 of 6	ENST00000369168.5	NP_000557.1	P12314-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCGR1A	ENST00000369168.5 link	c.274C>T	p.Arg92*	stop_gained	Exon 3 of 6	1	NM_000566.4	ENSP00000358165.4	P12314-1
FCGR1A	ENST00000444948.5 link	c.31+1450C>T		intron_variant	Intron 1 of 3	2		ENSP00000394279.1	C9JSN8
H2BC18	ENST00000545683.1 link	c.378-964G>A		intron_variant	Intron 1 of 1	2		ENSP00000445831.1	Q5QNW6-2
H2BC18	ENST00000420462.1 link	n.76-964G>A		intron_variant	Intron 1 of 1	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

GnomAD2 exomes

AF:

0.00410

AC:

1001

AN:

243930

AF XY:

0.00436

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 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

African (AFR)

AF:

0.00102

AC:

AN:

33400

American (AMR)

AF:

0.00309

AC:

138

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26132

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.00441

AC:

380

AN:

86164

European-Finnish (FIN)

AF:

0.000786

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00387

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00709

AC:

7878

AN:

1111828

Other (OTH)

AF:

0.00498

AC:

300

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

633

1267

1900

2534

3167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.00388

AC:

588

AN:

151424

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

262

AN XY:

73956

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

40872

American (AMR)

AF:

0.00439

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5142

South Asian (SAS)

AF:

0.00249

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000379

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00652

AC:

443

AN:

67994

Other (OTH)

AF:

0.00332

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

139

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:

0.00476

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: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

IGG receptor I, phagocytic, familial deficiency of

Pathogenic:1

Mar 15, 1995

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

FCGR1A-related disorder

Uncertain:1

Feb 21, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

not provided

Uncertain:1

Dec 18, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.090

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.052

PhyloP100

0.37

Vest4

0.51

GERP RS

3.1

Mutation Taster

=53/147

disease causing (ClinVar)

(source)

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

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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