NM_006725.5:c.673C>T

Variant names:

• chr11-61008737-C-T
• rs11230563
• NM_006725.5:c.673C>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.673C>T​(p.Arg225Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,606,102 control chromosomes in the GnomAD database, including 93,780 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.38 (12084 hom., cov: 34)
  • Exomes 𝑓: 0.33 (81696 hom.)
• Consequence: CD6 NM_006725.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.938
• Publications: 113 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=4.8583746E-4).
• BP6: Variant 11-61008737-C-T is Benign according to our data. Variant chr11-61008737-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060458.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD6	NM_006725.5	MANE Select	c.673C>T	p.Arg225Trp	missense	Exon 4 of 13	NP_006716.3	P30203-1
	CD6	NM_001254750.2		c.673C>T	p.Arg225Trp	missense	Exon 4 of 11	NP_001241679.1	P30203-4
	CD6	NM_001254751.2		c.673C>T	p.Arg225Trp	missense	Exon 4 of 11	NP_001241680.1	P30203-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD6	ENST00000313421.11	TSL:1 MANE Select	c.673C>T	p.Arg225Trp	missense	Exon 4 of 13	ENSP00000323280.7	P30203-1
	CD6	ENST00000352009.9	TSL:1	c.673C>T	p.Arg225Trp	missense	Exon 4 of 11	ENSP00000340628.5	P30203-4
	CD6	ENST00000452451.6	TSL:1	c.673C>T	p.Arg225Trp	missense	Exon 4 of 11	ENSP00000390676.2	P30203-5

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57913 AN: 152078 Hom.: 12070 Cov.: 34

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.392

GnomAD2 exomes AF: 0.308 AC: 72739 AN: 235972 AF XY: 0.307

Gnomad AFR exome AF: 0.559

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.330 AC: 479520 AN: 1453906 Hom.: 81696 Cov.: 59 AF XY: 0.327 AC XY: 236434 AN XY: 722380

African (AFR) AF: 0.563 AC: 18767 AN: 33314

American (AMR) AF: 0.269 AC: 11865 AN: 44054

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 7539 AN: 25952

East Asian (EAS) AF: 0.182 AC: 7193 AN: 39466

South Asian (SAS) AF: 0.233 AC: 19985 AN: 85630

European-Finnish (FIN) AF: 0.247 AC: 12764 AN: 51768

Middle Eastern (MID) AF: 0.400 AC: 2297 AN: 5746

European-Non Finnish (NFE) AF: 0.342 AC: 379422 AN: 1107950

Other (OTH) AF: 0.328 AC: 19688 AN: 60026

GnomAD4 genome AF: 0.381 AC: 57965 AN: 152196 Hom.: 12084 Cov.: 34 AF XY: 0.370 AC XY: 27528 AN XY: 74404

African (AFR) AF: 0.551 AC: 22874 AN: 41514

American (AMR) AF: 0.315 AC: 4824 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 952 AN: 3472

East Asian (EAS) AF: 0.178 AC: 923 AN: 5174

South Asian (SAS) AF: 0.218 AC: 1054 AN: 4826

European-Finnish (FIN) AF: 0.242 AC: 2570 AN: 10608

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23291 AN: 67980

Other (OTH) AF: 0.392 AC: 828 AN: 2114

Alfa AF: 0.351 Hom.: 40485

Bravo AF: 0.398

TwinsUK AF: 0.341 AC: 1263

ALSPAC AF: 0.351 AC: 1352

ESP6500AA AF: 0.541 AC: 2381

ESP6500EA AF: 0.333 AC: 2855

ExAC AF: 0.305 AC: 36568

Asia WGS AF: 0.241 AC: 840 AN: 3476

ClinVar

ClinVar submissions

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	0.29
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.00049	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.075	N
PhyloP100		0.94
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.077
Sift	Benign	0.17	T
Sift4G	Benign	0.072	T
Polyphen		0.37	B
Vest4		0.088
MPC		1.4
ClinPred		0.024	T
GERP RS		1.2
PromoterAI		-0.010	Neutral
Varity_R		0.51
gMVP		0.89
Mutation Taster		=99/1	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: rs11230563; hg19: chr11-60776209; COSMIC: COSV57835912; COSMIC: COSV57835912;