11-35180295-C-T

Variant summary

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

The NM_000610.4(CD44):c.255C>T(p.His85=) 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. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2182 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20027 hom.)
• Consequence: CD44 NM_000610.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 11-35180295-C-T is Benign according to our data. Variant chr11-35180295-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD44	NM_000610.4	c.255C>T	p.His85=	synonymous_variant	3/18	ENST00000428726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD44	ENST00000428726.8	c.255C>T	p.His85=	synonymous_variant	3/18	1	NM_000610.4	A2

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

GnomAD3 exomes AF: 0.162 AC: 40768 AN: 251238 Hom.: 3568 AF XY: 0.163 AC XY: 22143 AN XY: 135784

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 SAS exome AF: 0.142

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

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.0605

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.167

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

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0796

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.183

Alfa AF: 0.172 Hom.: 4236

Bravo AF: 0.172

Asia WGS AF: 0.105 AC: 363 AN: 3478

EpiCase AF: 0.186

EpiControl AF: 0.189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CD44-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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	-0.66
Cadd	Benign	5.1
Dann	Benign	0.76

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: rs1071695; hg19: chr11-35201842; COSMIC: COSV53534093; COSMIC: COSV53534093;