rs115855950

Variant names:

• chr1-159809674-T-C
• rs115855950
• NM_001004310.3:c.877T>C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004310.3. 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
	FCRL6	NM_001004310.3	MANE Select	c.877T>C	p.Ser293Pro	missense	Exon 5 of 10	NP_001004310.2
	FCRL6	NM_001426231.1		c.907T>C	p.Ser303Pro	missense	Exon 6 of 11	NP_001413160.1
	FCRL6	NM_001426232.1		c.898T>C	p.Ser300Pro	missense	Exon 6 of 11	NP_001413161.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL6	ENST00000368106.4	TSL:1 MANE Select	c.877T>C	p.Ser293Pro	missense	Exon 5 of 10	ENSP00000357086.3
	FCRL6	ENST00000339348.9	TSL:1	c.877T>C	p.Ser293Pro	missense	Exon 5 of 9	ENSP00000340949.5
	FCRL6	ENST00000392235.7	TSL:1	c.592T>C	p.Ser198Pro	missense	Exon 4 of 9	ENSP00000376068.3

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

GnomAD2 exomes AF: 0.0118 AC: 2962 AN: 250436 AF XY: 0.00872

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 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

African (AFR) AF: 0.154 AC: 5133 AN: 33438

American (AMR) AF: 0.00977 AC: 437 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86252

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53280

Middle Eastern (MID) AF: 0.0225 AC: 130 AN: 5768

European-Non Finnish (NFE) AF: 0.000390 AC: 434 AN: 1111906

Other (OTH) AF: 0.0106 AC: 639 AN: 60392

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

African (AFR) AF: 0.152 AC: 6287 AN: 41452

American (AMR) AF: 0.0156 AC: 239 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 67990

Other (OTH) AF: 0.0303 AC: 64 AN: 2110

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.033
Sift	Benign	0.22	T
Sift4G	Benign	0.088	T
Polyphen		0.079	B
Vest4		0.23
MPC		0.024
ClinPred		0.013	T
GERP RS		1.5
Varity_R		0.16
gMVP		0.40
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs115855950; hg19: chr1-159779464; COSMIC: COSV58939748; COSMIC: COSV58939748;