chr1-157802090-C-T

Variant names:

• chr1-157802090-C-T
• rs4971154
• NM_052938.5:c.711G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_052938.5(FCRL1):​c.711G>A​(p.Pro237Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,613,850 control chromosomes in the GnomAD database, including 203,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (15189 hom., cov: 32)
  • Exomes 𝑓: 0.50 (187869 hom.)
• Consequence: FCRL1 NM_052938.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.78
• Publications: 31 publications found

Genes affected

FCRL1 (HGNC:18509): (Fc receptor like 1) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains three extracellular C2-like immunoglobulin domains, a transmembrane domain and a cytoplasmic domain with two immunoreceptor-tyrosine activation motifs. This protein may play a role in the regulation of cancer cell growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-5.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052938.5. 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
	FCRL1	NM_052938.5	MANE Select	c.711G>A	p.Pro237Pro	synonymous	Exon 5 of 11	NP_443170.1
	FCRL1	NM_001159398.2		c.711G>A	p.Pro237Pro	synonymous	Exon 5 of 11	NP_001152870.1
	FCRL1	NM_001159397.2		c.711G>A	p.Pro237Pro	synonymous	Exon 5 of 10	NP_001152869.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL1	ENST00000368176.8	TSL:1 MANE Select	c.711G>A	p.Pro237Pro	synonymous	Exon 5 of 11	ENSP00000357158.3
	FCRL1	ENST00000491942.2	TSL:1	c.711G>A	p.Pro237Pro	synonymous	Exon 5 of 11	ENSP00000418130.1
	FCRL1	ENST00000368175.7	TSL:1	n.477G>A		non_coding_transcript_exon	Exon 5 of 11

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62264 AN: 151966 Hom.: 15180 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.423

GnomAD2 exomes AF: 0.494 AC: 123940 AN: 250862 AF XY: 0.502

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.495

Gnomad ASJ exome AF: 0.516

Gnomad EAS exome AF: 0.542

Gnomad FIN exome AF: 0.584

Gnomad NFE exome AF: 0.516

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.502 AC: 734195 AN: 1461766 Hom.: 187869 Cov.: 57 AF XY: 0.504 AC XY: 366767 AN XY: 727170

African (AFR) AF: 0.114 AC: 3811 AN: 33480

American (AMR) AF: 0.499 AC: 22298 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 13268 AN: 26134

East Asian (EAS) AF: 0.562 AC: 22320 AN: 39696

South Asian (SAS) AF: 0.513 AC: 44229 AN: 86248

European-Finnish (FIN) AF: 0.575 AC: 30697 AN: 53418

Middle Eastern (MID) AF: 0.476 AC: 2745 AN: 5768

European-Non Finnish (NFE) AF: 0.509 AC: 565747 AN: 1111916

Other (OTH) AF: 0.482 AC: 29080 AN: 60390

GnomAD4 genome AF: 0.410 AC: 62281 AN: 152084 Hom.: 15189 Cov.: 32 AF XY: 0.415 AC XY: 30834 AN XY: 74324

African (AFR) AF: 0.130 AC: 5414 AN: 41512

American (AMR) AF: 0.465 AC: 7110 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1766 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2805 AN: 5148

South Asian (SAS) AF: 0.503 AC: 2425 AN: 4822

European-Finnish (FIN) AF: 0.579 AC: 6124 AN: 10570

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35263 AN: 67964

Other (OTH) AF: 0.420 AC: 886 AN: 2112

Alfa AF: 0.443 Hom.: 6694

Bravo AF: 0.389

Asia WGS AF: 0.448 AC: 1557 AN: 3476

EpiCase AF: 0.514

EpiControl AF: 0.506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.086
DANN	Benign	0.45
PhyloP100		-5.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4971154; hg19: chr1-157771880; COSMIC: COSV63824383; COSMIC: COSV63824383;