rs4756196

Positions:

• chr11-35176561-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000428726.8(CD44):​c.68-14A>G variant causes a splice polypyrimidine tract, 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 ENST00000428726.8 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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 -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/exons	MANE	Protein	UniProt
CD44	NM_000610.4	c.68-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.68-14A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000610.4	ENSP00000398632	A2

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

GnomAD3 exomes AF: 0.524 AC: 126577 AN: 241600 Hom.: 34050 AF XY: 0.522 AC XY: 68309 AN XY: 130860

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 SAS exome AF: 0.568

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

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.513

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

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.568

Alfa AF: 0.515 Hom.: 42773

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

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: rs4756196; hg19: chr11-35198108; COSMIC: COSV53532771; COSMIC: COSV53532771;