Variant 1-157524453-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_031281.3(FCRL5):c.2065A>G(p.Ile689Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,152 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00070 ( 12 hom. )

Consequence

FCRL5
NM_031281.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.31

Variant links:

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]

FCRL5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006784886).

BP6

Variant 1-157524453-T-C is Benign according to our data. Variant chr1-157524453-T-C is described in ClinVar as [Benign]. Clinvar id is 709690.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00646 (984/152262) while in subpopulation AFR AF= 0.0228 (947/41556). AF 95% confidence interval is 0.0216. There are 11 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL5	NM_031281.3 linkuse as main transcript	c.2065A>G	p.Ile689Val	missense_variant	10/17	ENST00000361835.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL5	ENST00000361835.8 linkuse as main transcript	c.2065A>G	p.Ile689Val	missense_variant	10/17	1	NM_031281.3	P1	Q96RD9-1
FCRL5	ENST00000368190.7 linkuse as main transcript	c.2065A>G	p.Ile689Val	missense_variant	10/10	1			Q96RD9-3
FCRL5	ENST00000497286.5 linkuse as main transcript	n.1158A>G		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes

AF:

0.00647

AC:

985

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00165

AC:

414

AN:

251426

Hom.:

AF XY:

0.00108

AC XY:

147

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0234

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000698

AC:

1021

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

415

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0261

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00646

AC:

984

AN:

152262

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

475

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00137

Hom.:

Bravo

AF:

0.00728

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00210

AC:

255

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0016

T;.

Eigen

Benign

0.063

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0068

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.75

N;N

REVEL

Benign

0.19

Sift

Benign

0.17

T;D

Sift4G

Uncertain

0.011

D;T

Polyphen

1.0

D;B

Vest4

0.47

MVP

0.085

MPC

0.38

ClinPred

0.041

GERP RS

4.7

Varity_R

0.053

gMVP

0.066

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over