11-61008835-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_006725.5(CD6):c.771G>C(p.Ala257=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,541,770 control chromosomes in the GnomAD database, including 15,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2455 hom., cov: 34)
  • Exomes 𝑓: 0.13 (13050 hom.)
• Consequence: CD6 NM_006725.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.231

Genes affected

CD6 (HGNC:1691): (CD6 molecule) This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-61008835-G-C is Benign according to our data. Variant chr11-61008835-G-C is described in ClinVar as [Benign]. Clinvar id is 3059695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.231 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD6	NM_006725.5	c.771G>C	p.Ala257=	synonymous_variant	4/13	ENST00000313421.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD6	ENST00000313421.11	c.771G>C	p.Ala257=	synonymous_variant	4/13	1	NM_006725.5	P2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25085 AN: 152134 Hom.: 2453 Cov.: 34

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.128 AC: 24273 AN: 189930 Hom.: 1752 AF XY: 0.129 AC XY: 13202 AN XY: 102176

Gnomad AFR exome AF: 0.282

Gnomad AMR exome AF: 0.0917

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.0784

Gnomad SAS exome AF: 0.151

Gnomad FIN exome AF: 0.0780

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.133 AC: 185259 AN: 1389518 Hom.: 13050 Cov.: 39 AF XY: 0.135 AC XY: 91768 AN XY: 681770

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.0952

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0666

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.0809

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.165 AC: 25119 AN: 152252 Hom.: 2455 Cov.: 34 AF XY: 0.160 AC XY: 11932 AN XY: 74442

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0809

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0764

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0758 Hom.: 168

Bravo AF: 0.175

Asia WGS AF: 0.133 AC: 465 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CD6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	9.6
Dann	Benign	0.61

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: rs79848107; hg19: chr11-60776307; COSMIC: COSV57839152; COSMIC: COSV57839152;