rs3811035

chr1-157515771-G-Achr1-157515771-G-Cchr1-157515771-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031281.3(FCRL5):c.2845-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,613,542 control chromosomes in the GnomAD database, including 327,006 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (23970 hom., cov: 32)
  • Exomes 𝑓: 0.64 (303036 hom.)
• Consequence: FCRL5 NM_031281.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002593
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL5	NM_031281.3	c.2845-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361835.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL5	ENST00000361835.8	c.2845-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_031281.3	P1
FCRL5	ENST00000461387.5	n.2122-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2
FCRL5	ENST00000462218.1	n.233-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2
FCRL5	ENST00000497286.5	n.1938-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78579 AN: 151818 Hom.: 23959 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.531

GnomAD3 exomes AF: 0.634 AC: 159414 AN: 251336 Hom.: 53016 AF XY: 0.642 AC XY: 87204 AN XY: 135876

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.720

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.653

Gnomad SAS exome AF: 0.665

Gnomad FIN exome AF: 0.690

Gnomad NFE exome AF: 0.656

Gnomad OTH exome AF: 0.648

GnomAD4 exome AF: 0.638 AC: 932433 AN: 1461604 Hom.: 303036 Cov.: 52 AF XY: 0.640 AC XY: 465658 AN XY: 727120

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.666

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.517 AC: 78598 AN: 151938 Hom.: 23970 Cov.: 32 AF XY: 0.527 AC XY: 39110 AN XY: 74236

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.528

Alfa AF: 0.621 Hom.: 49105

Bravo AF: 0.498

Asia WGS AF: 0.630 AC: 2187 AN: 3478

EpiCase AF: 0.640

EpiControl AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs3811035; hg19: chr1-157485561;