1-157539092-C-T

Variant names:

• chr1-157539092-C-T
• rs6427384
• NM_031281.3:c.1396G>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.1396G>A​(p.Val466Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,612,654 control chromosomes in the GnomAD database, including 557,643 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 (42905 hom., cov: 34)
  • Exomes 𝑓: 0.84 (514738 hom.)
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• 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=1.2775563E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.847 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.1396G>A	p.Val466Ile	missense	Exon 7 of 17	NP_112571.2	Q96RD9-1
	FCRL5	NM_001195388.2		c.1396G>A	p.Val466Ile	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.1396G>A	p.Val466Ile	missense	Exon 7 of 17	ENSP00000354691.3	Q96RD9-1
	FCRL5	ENST00000368190.7	TSL:1	c.1396G>A	p.Val466Ile	missense	Exon 7 of 10	ENSP00000357173.3	Q96RD9-3
	FCRL5	ENST00000368189.3	TSL:1	c.1396G>A	p.Val466Ile	missense	Exon 7 of 8	ENSP00000357172.3	Q96RD9-4

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110067 AN: 152126 Hom.: 42910 Cov.: 34

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.767

GnomAD2 exomes AF: 0.820 AC: 204897 AN: 249900 AF XY: 0.831

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.828

Gnomad ASJ exome AF: 0.875

Gnomad EAS exome AF: 0.780

Gnomad FIN exome AF: 0.884

Gnomad NFE exome AF: 0.857

Gnomad OTH exome AF: 0.848

GnomAD4 exome AF: 0.836 AC: 1221158 AN: 1460410 Hom.: 514738 Cov.: 56 AF XY: 0.839 AC XY: 609523 AN XY: 726450

African (AFR) AF: 0.379 AC: 12691 AN: 33452

American (AMR) AF: 0.825 AC: 36876 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 22724 AN: 26062

East Asian (EAS) AF: 0.761 AC: 30191 AN: 39686

South Asian (SAS) AF: 0.859 AC: 73980 AN: 86080

European-Finnish (FIN) AF: 0.882 AC: 47080 AN: 53350

Middle Eastern (MID) AF: 0.851 AC: 4533 AN: 5324

European-Non Finnish (NFE) AF: 0.849 AC: 943751 AN: 1111476

Other (OTH) AF: 0.818 AC: 49332 AN: 60298

GnomAD4 genome AF: 0.723 AC: 110081 AN: 152244 Hom.: 42905 Cov.: 34 AF XY: 0.727 AC XY: 54131 AN XY: 74438

African (AFR) AF: 0.401 AC: 16637 AN: 41510

American (AMR) AF: 0.798 AC: 12223 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3037 AN: 3472

East Asian (EAS) AF: 0.776 AC: 4022 AN: 5180

South Asian (SAS) AF: 0.859 AC: 4147 AN: 4828

European-Finnish (FIN) AF: 0.884 AC: 9381 AN: 10608

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58015 AN: 68012

Other (OTH) AF: 0.766 AC: 1621 AN: 2116

Alfa AF: 0.812 Hom.: 167153

Bravo AF: 0.702

TwinsUK AF: 0.854 AC: 3168

ALSPAC AF: 0.853 AC: 3286

ESP6500AA AF: 0.408 AC: 1796

ESP6500EA AF: 0.849 AC: 7298

ExAC AF: 0.813 AC: 98734

Asia WGS AF: 0.784 AC: 2727 AN: 3478

EpiCase AF: 0.855

EpiControl AF: 0.852

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.011
DANN	Benign	0.97
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.0080
Sift	Benign	0.34	T
Sift4G	Benign	0.35	T
Polyphen		0.13	B
Vest4		0.048
MPC		0.060
ClinPred		0.0063	T
GERP RS		-1.7
Varity_R		0.067
gMVP		0.094
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6427384; hg19: chr1-157508882; COSMIC: COSV62515391; COSMIC: COSV62515391;