1-157524427-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_031281.3(FCRL5):c.2091T>C(p.Asp697=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,614,226 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (63 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (55 hom.)
• Consequence: FCRL5 NM_031281.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.452

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-157524427-A-G is Benign according to our data. Variant chr1-157524427-A-G is described in ClinVar as [Benign]. Clinvar id is 784957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.452 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL5	NM_031281.3	c.2091T>C	p.Asp697=	synonymous_variant	10/17	ENST00000361835.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL5	ENST00000361835.8	c.2091T>C	p.Asp697=	synonymous_variant	10/17	1	NM_031281.3	P1
FCRL5	ENST00000368190.7	c.2091T>C	p.Asp697=	synonymous_variant	10/10	1
FCRL5	ENST00000497286.5	n.1184T>C		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2309 AN: 152214 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00436 AC: 1096 AN: 251462 Hom.: 23 AF XY: 0.00328 AC XY: 446 AN XY: 135904

Gnomad AFR exome AF: 0.0533

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.00446

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00173 AC: 2536 AN: 1461894 Hom.: 55 Cov.: 31 AF XY: 0.00153 AC XY: 1112 AN XY: 727248

Gnomad4 AFR exome AF: 0.0530

Gnomad4 AMR exome AF: 0.00414

Gnomad4 ASJ exome AF: 0.00367

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000170

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.0152 AC: 2322 AN: 152332 Hom.: 63 Cov.: 33 AF XY: 0.0154 AC XY: 1144 AN XY: 74492

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.00843

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00753 Hom.: 10

Bravo AF: 0.0174

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs76824212; hg19: chr1-157494217;