1-157539235-C-T

Variant names:

• chr1-157539235-C-T
• rs2012199
• NM_031281.3:c.1253G>A

Variant summary

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

The NM_031281.3(FCRL5):​c.1253G>A​(p.Gly418Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,614,010 control chromosomes in the GnomAD database, including 593,475 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G418S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.83 (53241 hom., cov: 33)
  • Exomes 𝑓: 0.86 (540234 hom.)
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=9.567752E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL5	NM_031281.3	c.1253G>A	p.Gly418Asp	missense_variant	Exon 7 of 17	ENST00000361835.8	NP_112571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL5	ENST00000361835.8	c.1253G>A	p.Gly418Asp	missense_variant	Exon 7 of 17	1	NM_031281.3	ENSP00000354691.3
FCRL5	ENST00000368190.7	c.1253G>A	p.Gly418Asp	missense_variant	Exon 7 of 10	1		ENSP00000357173.3
FCRL5	ENST00000368189.3	c.1253G>A	p.Gly418Asp	missense_variant	Exon 7 of 8	1		ENSP00000357172.3

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126984 AN: 152080 Hom.: 53211 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.850

GnomAD2 exomes AF: 0.867 AC: 217521 AN: 251028 AF XY: 0.871

Gnomad AFR exome AF: 0.754

Gnomad AMR exome AF: 0.852

Gnomad ASJ exome AF: 0.891

Gnomad EAS exome AF: 0.876

Gnomad FIN exome AF: 0.887

Gnomad NFE exome AF: 0.865

Gnomad OTH exome AF: 0.874

GnomAD4 exome AF: 0.859 AC: 1255965 AN: 1461812 Hom.: 540234 Cov.: 65 AF XY: 0.862 AC XY: 626741 AN XY: 727208

Gnomad4 AFR exome AF: 0.749 AC: 25072 AN: 33476

Gnomad4 AMR exome AF: 0.852 AC: 38080 AN: 44720

Gnomad4 ASJ exome AF: 0.887 AC: 23193 AN: 26134

Gnomad4 EAS exome AF: 0.841 AC: 33368 AN: 39690

Gnomad4 SAS exome AF: 0.914 AC: 78856 AN: 86250

Gnomad4 FIN exome AF: 0.886 AC: 47335 AN: 53418

Gnomad4 NFE exome AF: 0.857 AC: 953025 AN: 1111960

Gnomad4 Remaining exome AF: 0.860 AC: 51929 AN: 60396

GnomAD4 genome AF: 0.835 AC: 127071 AN: 152198 Hom.: 53241 Cov.: 33 AF XY: 0.837 AC XY: 62286 AN XY: 74418

Gnomad4 AFR AF: 0.754 AC: 0.753625 AN: 0.753625

Gnomad4 AMR AF: 0.842 AC: 0.841703 AN: 0.841703

Gnomad4 ASJ AF: 0.889 AC: 0.889401 AN: 0.889401

Gnomad4 EAS AF: 0.870 AC: 0.869624 AN: 0.869624

Gnomad4 SAS AF: 0.922 AC: 0.921992 AN: 0.921992

Gnomad4 FIN AF: 0.887 AC: 0.887358 AN: 0.887358

Gnomad4 NFE AF: 0.863 AC: 0.862671 AN: 0.862671

Gnomad4 OTH AF: 0.850 AC: 0.849763 AN: 0.849763

Alfa AF: 0.854 Hom.: 231208

Bravo AF: 0.826

TwinsUK AF: 0.862 AC: 3195

ALSPAC AF: 0.862 AC: 3321

ESP6500AA AF: 0.761 AC: 3352

ESP6500EA AF: 0.857 AC: 7370

ExAC AF: 0.867 AC: 105213

Asia WGS AF: 0.888 AC: 3087 AN: 3478

EpiCase AF: 0.863

EpiControl AF: 0.861

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.027
DANN	Benign	0.078
DEOGEN2	Benign	0.0032	T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.17	T;T;T
MetaRNN	Benign	9.6e-7	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.67	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.48	N;N;N
REVEL	Benign	0.016
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.70	T;T;T
Polyphen		0.010	B;B;B
Vest4		0.080
MPC		0.086
ClinPred		0.0064	T
GERP RS		-3.8
Varity_R		0.061
gMVP		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2012199; hg19: chr1-157509025; COSMIC: COSV62518084; COSMIC: COSV62518084;