1-157521276-C-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.2256G>C(p.Pro752=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,609,076 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (68 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (69 hom.)
• Consequence: FCRL5 NM_031281.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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=-0.88).
• BP6: Variant 1-157521276-C-G is Benign according to our data. Variant chr1-157521276-C-G is described in ClinVar as [Benign]. Clinvar id is 784956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL5	NM_031281.3	c.2256G>C	p.Pro752=	synonymous_variant	11/17	ENST00000361835.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL5	ENST00000361835.8	c.2256G>C	p.Pro752=	synonymous_variant	11/17	1	NM_031281.3	P1
FCRL5	ENST00000461387.5	n.1519G>C		non_coding_transcript_exon_variant	1/7	2
FCRL5	ENST00000497286.5	n.1349G>C		non_coding_transcript_exon_variant	3/9	2

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2508 AN: 152142 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00936

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: 0.000206

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00466 AC: 1133 AN: 242962 Hom.: 37 AF XY: 0.00334 AC XY: 441 AN XY: 132054

Gnomad AFR exome AF: 0.0579

Gnomad AMR exome AF: 0.00447

Gnomad ASJ exome AF: 0.00466

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000201

Gnomad OTH exome AF: 0.00187

GnomAD4 exome AF: 0.00184 AC: 2681 AN: 1456816 Hom.: 69 Cov.: 32 AF XY: 0.00158 AC XY: 1142 AN XY: 724688

Gnomad4 AFR exome AF: 0.0579

Gnomad4 AMR exome AF: 0.00477

Gnomad4 ASJ exome AF: 0.00366

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000164

Gnomad4 OTH exome AF: 0.00417

GnomAD4 genome AF: 0.0165 AC: 2515 AN: 152260 Hom.: 68 Cov.: 33 AF XY: 0.0166 AC XY: 1233 AN XY: 74454

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.00929

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.0186

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000218

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

Jul 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.024
Dann	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs74858059; hg19: chr1-157491066;