Genetic Variant FCRL6:p.Asp158Asp (chr1-159809115-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001004310.3(FCRL6):c.474C>T(p.Asp158Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,614,108 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 6 hom. )

Consequence

FCRL6
NM_001004310.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.115

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-159809115-C-T is Benign according to our data. Variant chr1-159809115-C-T is described in ClinVar as [Benign]. Clinvar id is 717386.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.115 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL6	NM_001004310.3 link	c.474C>T	p.Asp158Asp	synonymous_variant	Exon 4 of 10	ENST00000368106.4	NP_001004310.2	Q6DN72-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL6	ENST00000368106.4 link	c.474C>T	p.Asp158Asp	synonymous_variant	Exon 4 of 10	1	NM_001004310.3	ENSP00000357086.3		Q6DN72-1

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00224

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000883

AC:

222

AN:

251296

Hom.:

AF XY:

0.000965

AC XY:

131

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00178

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00227

AC:

3314

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

1574

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00281

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

152290

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00224

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00118

EpiCase

AF:

0.00153

EpiControl

AF:

0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.6

DANN

Benign

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over