rs115855950

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.19

Publications

4 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL6	NM_001004310.3 link	c.877T>C	p.Ser293Pro	missense_variant	Exon 5 of 10	ENST00000368106.4	NP_001004310.2	Q6DN72-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCRL6	ENST00000368106.4 link	c.877T>C	p.Ser293Pro	missense_variant	Exon 5 of 10	1	NM_001004310.3	ENSP00000357086.3	Q6DN72-1
FCRL6	ENST00000339348.9 link	c.877T>C	p.Ser293Pro	missense_variant	Exon 5 of 9	1		ENSP00000340949.5	Q6DN72-3
FCRL6	ENST00000392235.7 link	c.592T>C	p.Ser198Pro	missense_variant	Exon 4 of 9	1		ENSP00000376068.3	Q6DN72-4
FCRL6	ENST00000321935.10 link	c.898T>C	p.Ser300Pro	missense_variant	Exon 6 of 11	2		ENSP00000320625.6	Q6DN72-2

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6622

AN:

152022

Hom.:

466

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00407

AC XY:

2959

AN XY:

727106

show subpopulations

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:

AN:

26126

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.000417

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000188

AC:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

285

571

856

1142

1427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0436

AC:

6639

AN:

152140

Hom.:

468

Cov.:

AF XY:

0.0411

AC XY:

3060

AN XY:

74386

show subpopulations

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:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5164

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

67990

Other (OTH)

AF:

0.0303

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

278

555

833

1110

1388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0212

Hom.:

Bravo

AF:

0.0491

ExAC

AF:

0.0148

AC:

1798

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.9

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0061

.;.;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.45

T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.1

.;M;.;M

PhyloP100

1.2

PrimateAI

Benign

0.29

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

GERP RS

1.5

Varity_R

0.16

gMVP

0.40

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over