rs115855950

Positions:

• chr1-159809674-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001004310.3(FCRL6):​c.877T>C​(p.Ser293Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00834 in 1,613,720 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (468 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (418 hom.)
• Consequence: FCRL6 NM_001004310.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.19

Genes affected

FCRL6 (HGNC:31910): (Fc receptor like 6) Enables MHC class II protein binding activity and protein phosphatase binding activity. Predicted to be involved in cell surface receptor signaling pathway. Located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FCRL6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019312501).
• BP6: Variant 1-159809674-T-C is Benign according to our data. Variant chr1-159809674-T-C is described in ClinVar as [Benign]. Clinvar id is 402860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL6	NM_001004310.3	c.877T>C	p.Ser293Pro	missense_variant	5/10	ENST00000368106.4	NP_001004310.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL6	ENST00000368106.4	c.877T>C	p.Ser293Pro	missense_variant	5/10	1	NM_001004310.3	ENSP00000357086.3
FCRL6	ENST00000339348.9	c.877T>C	p.Ser293Pro	missense_variant	5/9	1		ENSP00000340949.5
FCRL6	ENST00000392235.7	c.592T>C	p.Ser198Pro	missense_variant	4/9	1		ENSP00000376068.3
FCRL6	ENST00000321935.10	c.898T>C	p.Ser300Pro	missense_variant	6/11	2		ENSP00000320625.6

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6622 AN: 152022 Hom.: 466 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0307

GnomAD3 exomes AF: 0.0118 AC: 2962 AN: 250436 Hom.: 196 AF XY: 0.00872 AC XY: 1180 AN XY: 135398

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.00874

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000512

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.00466 AC: 6813 AN: 1461580 Hom.: 418 Cov.: 34 AF XY: 0.00407 AC XY: 2959 AN XY: 727106

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.00977

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000390

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0436 AC: 6639 AN: 152140 Hom.: 468 Cov.: 32 AF XY: 0.0411 AC XY: 3060 AN XY: 74386

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0212 Hom.: 81

Bravo AF: 0.0491

ExAC AF: 0.0148 AC: 1798

Asia WGS AF: 0.0120 AC: 44 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.9
DANN	Benign	0.88
DEOGEN2	Benign	0.0061	.;.;.;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.45	T;T;T;T
MetaRNN	Benign	0.0019	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	.;M;.;M
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.088	T;T;T;T
Polyphen		0.079	B;P;P;B
Vest4		0.23
MPC		0.024
ClinPred		0.013	T
GERP RS		1.5
Varity_R		0.16
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs115855950; hg19: chr1-159779464; COSMIC: COSV58939748; COSMIC: COSV58939748;