11-61009601-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006725.5(CD6):c.811G>A(p.Ala271Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,610,542 control chromosomes in the GnomAD database, including 23,669 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1737 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21932 hom.)
• Consequence: CD6 NM_006725.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.36

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018762946).
• BP6: Variant 11-61009601-G-A is Benign according to our data. Variant chr11-61009601-G-A is described in ClinVar as [Benign]. Clinvar id is 3060441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD6	NM_006725.5	c.811G>A	p.Ala271Thr	missense_variant	5/13	ENST00000313421.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD6	ENST00000313421.11	c.811G>A	p.Ala271Thr	missense_variant	5/13	1	NM_006725.5	P2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20466 AN: 152148 Hom.: 1733 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0607

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.153

GnomAD3 exomes AF: 0.132 AC: 32458 AN: 246532 Hom.: 2741 AF XY: 0.134 AC XY: 17900 AN XY: 133560

Gnomad AFR exome AF: 0.0560

Gnomad AMR exome AF: 0.0948

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.000327

Gnomad SAS exome AF: 0.0663

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.166 AC: 241861 AN: 1458276 Hom.: 21932 Cov.: 33 AF XY: 0.164 AC XY: 118766 AN XY: 725300

Gnomad4 AFR exome AF: 0.0535

Gnomad4 AMR exome AF: 0.0986

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.000328

Gnomad4 SAS exome AF: 0.0655

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.134 AC: 20474 AN: 152266 Hom.: 1737 Cov.: 32 AF XY: 0.130 AC XY: 9696 AN XY: 74456

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.151

Alfa AF: 0.165 Hom.: 1537

Bravo AF: 0.134

TwinsUK AF: 0.194 AC: 721

ALSPAC AF: 0.186 AC: 716

ESP6500AA AF: 0.0606 AC: 267

ESP6500EA AF: 0.182 AC: 1562

ExAC AF: 0.133 AC: 16168

Asia WGS AF: 0.0360 AC: 128 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

Dec 03, 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
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.030
Dann	Benign	0.76
DEOGEN2	Benign	0.00094	T;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.61	T;T;T
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.025	N;N;N
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.060
Sift	Benign	0.75	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.041	B;B;B
Vest4		0.092
MPC		0.96
ClinPred		0.011	T
GERP RS		-9.8
Varity_R		0.10
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12360861; hg19: chr11-60777073; COSMIC: COSV57838629; COSMIC: COSV57838629;