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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Publications: 40 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=9.567752E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL5	NM_031281.3	MANE Select	c.1253G>A	p.Gly418Asp	missense	Exon 7 of 17	NP_112571.2
	FCRL5	NM_001195388.2		c.1253G>A	p.Gly418Asp	missense	Exon 7 of 17	NP_001182317.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL5	ENST00000361835.8	TSL:1 MANE Select	c.1253G>A	p.Gly418Asp	missense	Exon 7 of 17	ENSP00000354691.3
	FCRL5	ENST00000368190.7	TSL:1	c.1253G>A	p.Gly418Asp	missense	Exon 7 of 10	ENSP00000357173.3
	FCRL5	ENST00000368189.3	TSL:1	c.1253G>A	p.Gly418Asp	missense	Exon 7 of 8	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

African (AFR) AF: 0.749 AC: 25072 AN: 33476

American (AMR) AF: 0.852 AC: 38080 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 23193 AN: 26134

East Asian (EAS) AF: 0.841 AC: 33368 AN: 39690

South Asian (SAS) AF: 0.914 AC: 78856 AN: 86250

European-Finnish (FIN) AF: 0.886 AC: 47335 AN: 53418

Middle Eastern (MID) AF: 0.885 AC: 5107 AN: 5768

European-Non Finnish (NFE) AF: 0.857 AC: 953025 AN: 1111960

Other (OTH) 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

African (AFR) AF: 0.754 AC: 31292 AN: 41522

American (AMR) AF: 0.842 AC: 12873 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3088 AN: 3472

East Asian (EAS) AF: 0.870 AC: 4489 AN: 5162

South Asian (SAS) AF: 0.922 AC: 4444 AN: 4820

European-Finnish (FIN) AF: 0.887 AC: 9406 AN: 10600

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58672 AN: 68012

Other (OTH) AF: 0.850 AC: 1793 AN: 2110

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 v4.9

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
MetaRNN	Benign	9.6e-7	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.67	N
PhyloP100		-1.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	0.70	T
Polyphen		0.010	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

Other links and lift over

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