chr1-157544307-A-G

Variant names:

• chr1-157544307-A-G
• rs6679793
• NM_031281.3:c.799T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031281.3(FCRL5):​c.799T>C​(p.Tyr267His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,613,752 control chromosomes in the GnomAD database, including 516,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (40878 hom., cov: 33)
  • Exomes 𝑓: 0.80 (475129 hom.)
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 38 publications found

Genes affected

FCRL5 (HGNC:18508): (Fc receptor like 5) This gene encodes a member of the immunoglobulin receptor superfamily and the Fc-receptor like family. This gene and several other Fc receptor-like gene members are clustered on the long arm of chromosome 1. The encoded protein is a single-pass type I membrane protein and contains 8 immunoglobulin-like C2-type domains. This gene is implicated in B cell development and lymphomagenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.5442423E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL5	NM_031281.3	c.799T>C	p.Tyr267His	missense_variant	Exon 5 of 17	ENST00000361835.8	NP_112571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL5	ENST00000361835.8	c.799T>C	p.Tyr267His	missense_variant	Exon 5 of 17	1	NM_031281.3	ENSP00000354691.3
FCRL5	ENST00000368190.7	c.799T>C	p.Tyr267His	missense_variant	Exon 5 of 10	1		ENSP00000357173.3
FCRL5	ENST00000368189.3	c.799T>C	p.Tyr267His	missense_variant	Exon 5 of 8	1		ENSP00000357172.3
FCRL5	ENST00000481082.1	n.997T>C		non_coding_transcript_exon_variant	Exon 6 of 7	2

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108896 AN: 151986 Hom.: 40889 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.745

GnomAD2 exomes AF: 0.784 AC: 196913 AN: 251172 AF XY: 0.791

Gnomad AFR exome AF: 0.460

Gnomad AMR exome AF: 0.728

Gnomad ASJ exome AF: 0.806

Gnomad EAS exome AF: 0.901

Gnomad FIN exome AF: 0.849

Gnomad NFE exome AF: 0.817

Gnomad OTH exome AF: 0.799

GnomAD4 exome AF: 0.804 AC: 1174775 AN: 1461648 Hom.: 475129 Cov.: 57 AF XY: 0.804 AC XY: 584607 AN XY: 727120

African (AFR) AF: 0.453 AC: 15156 AN: 33466

American (AMR) AF: 0.729 AC: 32618 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 21208 AN: 26134

East Asian (EAS) AF: 0.915 AC: 36340 AN: 39700

South Asian (SAS) AF: 0.768 AC: 66234 AN: 86252

European-Finnish (FIN) AF: 0.846 AC: 45210 AN: 53420

Middle Eastern (MID) AF: 0.736 AC: 4248 AN: 5768

European-Non Finnish (NFE) AF: 0.815 AC: 906118 AN: 1111792

Other (OTH) AF: 0.789 AC: 47643 AN: 60392

GnomAD4 genome AF: 0.716 AC: 108898 AN: 152104 Hom.: 40878 Cov.: 33 AF XY: 0.717 AC XY: 53306 AN XY: 74350

African (AFR) AF: 0.469 AC: 19440 AN: 41454

American (AMR) AF: 0.730 AC: 11156 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2807 AN: 3470

East Asian (EAS) AF: 0.902 AC: 4653 AN: 5160

South Asian (SAS) AF: 0.774 AC: 3736 AN: 4824

European-Finnish (FIN) AF: 0.846 AC: 8953 AN: 10586

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55576 AN: 68002

Other (OTH) AF: 0.746 AC: 1578 AN: 2116

Alfa AF: 0.786 Hom.: 214646

Bravo AF: 0.698

TwinsUK AF: 0.821 AC: 3046

ALSPAC AF: 0.819 AC: 3155

ESP6500AA AF: 0.474 AC: 2089

ESP6500EA AF: 0.813 AC: 6990

ExAC AF: 0.781 AC: 94847

Asia WGS AF: 0.809 AC: 2815 AN: 3478

EpiCase AF: 0.808

EpiControl AF: 0.805

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0050
DANN	Benign	0.20
DEOGEN2	Benign	0.00096	T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.30	T;T;T
MetaRNN	Benign	0.0000025	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.4	N;N;N
PhyloP100		-2.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.1	N;N;N
REVEL	Benign	0.012
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.048
MPC		0.086
ClinPred		0.00053	T
GERP RS		-6.0
Varity_R		0.014
gMVP		0.16
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs6679793; hg19: chr1-157514097; COSMIC: COSV62511010;