chr11-61008714-C-T

Variant names:

• chr11-61008714-C-T
• rs11230562
• NM_006725.5:c.650C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_006725.5(CD6):​c.650C>T​(p.Thr217Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,606,434 control chromosomes in the GnomAD database, including 38,470 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T217R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.16 (2685 hom., cov: 34)
  • Exomes 𝑓: 0.21 (35785 hom.)
• Consequence: CD6 NM_006725.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.764
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005012661).
• BP6: Variant 11-61008714-C-T is Benign according to our data. Variant chr11-61008714-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056065.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006725.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD6	NM_006725.5	MANE Select	c.650C>T	p.Thr217Met	missense	Exon 4 of 13	NP_006716.3
	CD6	NM_001254750.2		c.650C>T	p.Thr217Met	missense	Exon 4 of 11	NP_001241679.1
	CD6	NM_001254751.2		c.650C>T	p.Thr217Met	missense	Exon 4 of 11	NP_001241680.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD6	ENST00000313421.11	TSL:1 MANE Select	c.650C>T	p.Thr217Met	missense	Exon 4 of 13	ENSP00000323280.7
	CD6	ENST00000352009.9	TSL:1	c.650C>T	p.Thr217Met	missense	Exon 4 of 11	ENSP00000340628.5
	CD6	ENST00000452451.6	TSL:1	c.650C>T	p.Thr217Met	missense	Exon 4 of 11	ENSP00000390676.2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24160 AN: 152160 Hom.: 2685 Cov.: 34

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.206

GnomAD2 exomes AF: 0.171 AC: 39518 AN: 230678 AF XY: 0.174

Gnomad AFR exome AF: 0.0430

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.0248

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.211 AC: 306953 AN: 1454156 Hom.: 35785 Cov.: 46 AF XY: 0.209 AC XY: 151022 AN XY: 722760

African (AFR) AF: 0.0375 AC: 1252 AN: 33390

American (AMR) AF: 0.118 AC: 5169 AN: 43936

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 11133 AN: 25968

East Asian (EAS) AF: 0.0237 AC: 933 AN: 39446

South Asian (SAS) AF: 0.0776 AC: 6628 AN: 85410

European-Finnish (FIN) AF: 0.173 AC: 8915 AN: 51450

Middle Eastern (MID) AF: 0.319 AC: 1835 AN: 5754

European-Non Finnish (NFE) AF: 0.233 AC: 258473 AN: 1108774

Other (OTH) AF: 0.210 AC: 12615 AN: 60028

GnomAD4 genome AF: 0.159 AC: 24145 AN: 152278 Hom.: 2685 Cov.: 34 AF XY: 0.155 AC XY: 11576 AN XY: 74460

African (AFR) AF: 0.0437 AC: 1815 AN: 41572

American (AMR) AF: 0.154 AC: 2350 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3468

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5178

South Asian (SAS) AF: 0.0718 AC: 347 AN: 4830

European-Finnish (FIN) AF: 0.167 AC: 1772 AN: 10616

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15509 AN: 67992

Other (OTH) AF: 0.203 AC: 428 AN: 2112

Alfa AF: 0.227 Hom.: 4854

Bravo AF: 0.156

TwinsUK AF: 0.242 AC: 899

ALSPAC AF: 0.229 AC: 883

ESP6500AA AF: 0.0542 AC: 238

ESP6500EA AF: 0.238 AC: 2045

ExAC AF: 0.161 AC: 19349

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CD6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	N
PhyloP100		0.76
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.046
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.075
MPC		2.0
ClinPred		0.012	T
GERP RS		0.67
PromoterAI		0.00010	Neutral
Varity_R		0.20
gMVP		0.68
Mutation Taster		=100/0	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: rs11230562; hg19: chr11-60776186; COSMIC: COSV57836892; COSMIC: COSV57836892;