11-35180295-C-T

Variant names:

• chr11-35180295-C-T
• rs1071695
• NM_000610.4:c.255C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BA1

The NM_000610.4(CD44):​c.255C>T​(p.His85His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,426 control chromosomes in the GnomAD database, including 22,209 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2182 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20027 hom.)
• Consequence: CD44 NM_000610.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -2.44
• Publications: 22 publications found

Genes affected

CD44 (HGNC:1681): (CD44 molecule (IN blood group)) The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP6: Variant 11-35180295-C-T is Benign according to our data. Variant chr11-35180295-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3059200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000610.4. 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
	CD44	NM_000610.4	MANE Select	c.255C>T	p.His85His	synonymous	Exon 3 of 18	NP_000601.3
	CD44	NM_001440324.1		c.255C>T	p.His85His	synonymous	Exon 3 of 18	NP_001427253.1
	CD44	NM_001440325.1		c.255C>T	p.His85His	synonymous	Exon 3 of 18	NP_001427254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.255C>T	p.His85His	synonymous	Exon 3 of 18	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.255C>T	p.His85His	synonymous	Exon 3 of 17	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.255C>T	p.His85His	synonymous	Exon 3 of 12	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24972 AN: 151992 Hom.: 2176 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.162 AC: 40768 AN: 251238 AF XY: 0.163

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.0811

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.189

GnomAD4 exome AF: 0.161 AC: 235773 AN: 1461316 Hom.: 20027 Cov.: 33 AF XY: 0.162 AC XY: 117637 AN XY: 727006

African (AFR) AF: 0.162 AC: 5423 AN: 33460

American (AMR) AF: 0.212 AC: 9461 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 6461 AN: 26124

East Asian (EAS) AF: 0.0605 AC: 2400 AN: 39696

South Asian (SAS) AF: 0.142 AC: 12240 AN: 86248

European-Finnish (FIN) AF: 0.110 AC: 5869 AN: 53418

Middle Eastern (MID) AF: 0.276 AC: 1592 AN: 5768

European-Non Finnish (NFE) AF: 0.164 AC: 182274 AN: 1111512

Other (OTH) AF: 0.167 AC: 10053 AN: 60376

GnomAD4 genome AF: 0.164 AC: 25009 AN: 152110 Hom.: 2182 Cov.: 31 AF XY: 0.162 AC XY: 12054 AN XY: 74342

African (AFR) AF: 0.157 AC: 6504 AN: 41474

American (AMR) AF: 0.221 AC: 3375 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3470

East Asian (EAS) AF: 0.0796 AC: 411 AN: 5164

South Asian (SAS) AF: 0.123 AC: 593 AN: 4822

European-Finnish (FIN) AF: 0.0939 AC: 995 AN: 10596

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11602 AN: 67980

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.170 Hom.: 8793

Bravo AF: 0.172

Asia WGS AF: 0.105 AC: 363 AN: 3478

EpiCase AF: 0.186

EpiControl AF: 0.189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CD44-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.1
DANN	Benign	0.76
PhyloP100		-2.4
PromoterAI		-0.059	Neutral
Mutation Taster		=98/2	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: rs1071695; hg19: chr11-35201842; COSMIC: COSV53534093; COSMIC: COSV53534093;