rs4756196

Variant names:

• chr11-35176561-A-G
• rs4756196
• NM_000610.4:c.68-14A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000610.4(CD44):​c.68-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,599,148 control chromosomes in the GnomAD database, including 214,065 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (24764 hom., cov: 33)
  • Exomes 𝑓: 0.51 (189301 hom.)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 19 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.68-14A>G		intron_variant	Intron 1 of 17	ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.68-14A>G		intron_variant	Intron 1 of 17	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84988 AN: 152030 Hom.: 24711 Cov.: 33

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.565

GnomAD2 exomes AF: 0.524 AC: 126577 AN: 241600 AF XY: 0.522

Gnomad AFR exome AF: 0.706

Gnomad AMR exome AF: 0.626

Gnomad ASJ exome AF: 0.513

Gnomad EAS exome AF: 0.303

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.508

Gnomad OTH exome AF: 0.531

GnomAD4 exome AF: 0.508 AC: 734495 AN: 1447000 Hom.: 189301 Cov.: 29 AF XY: 0.508 AC XY: 365843 AN XY: 719854

African (AFR) AF: 0.714 AC: 23292 AN: 32640

American (AMR) AF: 0.622 AC: 26332 AN: 42334

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 13191 AN: 25520

East Asian (EAS) AF: 0.304 AC: 12037 AN: 39532

South Asian (SAS) AF: 0.566 AC: 47999 AN: 84866

European-Finnish (FIN) AF: 0.452 AC: 24013 AN: 53168

Middle Eastern (MID) AF: 0.571 AC: 3255 AN: 5704

European-Non Finnish (NFE) AF: 0.502 AC: 553784 AN: 1103546

Other (OTH) AF: 0.513 AC: 30592 AN: 59690

GnomAD4 genome AF: 0.559 AC: 85112 AN: 152148 Hom.: 24764 Cov.: 33 AF XY: 0.556 AC XY: 41386 AN XY: 74382

African (AFR) AF: 0.706 AC: 29313 AN: 41526

American (AMR) AF: 0.589 AC: 9009 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1792 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1592 AN: 5180

South Asian (SAS) AF: 0.539 AC: 2602 AN: 4828

European-Finnish (FIN) AF: 0.439 AC: 4638 AN: 10558

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34331 AN: 67972

Other (OTH) AF: 0.568 AC: 1200 AN: 2112

Alfa AF: 0.523 Hom.: 89469

Bravo AF: 0.573

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.42
PhyloP100		-1.0
PromoterAI		0.020	Neutral
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: rs4756196; hg19: chr11-35198108; COSMIC: COSV53532771; COSMIC: COSV53532771;