rs7116432

chr11-35222511-A-Gchr11-35222511-A-T

Variant summary

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

The ENST00000442151.6(CD44):c.*133A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,097,788 control chromosomes in the GnomAD database, including 71,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (10262 hom., cov: 29)
  • Exomes 𝑓: 0.35 (60754 hom.)
• Consequence: CD44 ENST00000442151.6 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.322

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD44	NM_000610.4	c.2024+779A>G		intron_variant		ENST00000428726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD44	ENST00000428726.8	c.2024+779A>G		intron_variant		1	NM_000610.4	A2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52685 AN: 151064 Hom.: 10267 Cov.: 29

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.351 AC: 332511 AN: 946626 Hom.: 60754 Cov.: 19 AF XY: 0.355 AC XY: 160490 AN XY: 452076

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.820

Gnomad4 SAS exome AF: 0.533

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.349 AC: 52685 AN: 151162 Hom.: 10262 Cov.: 29 AF XY: 0.359 AC XY: 26519 AN XY: 73834

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.348

Alfa AF: 0.342 Hom.: 8907

Bravo AF: 0.350

Asia WGS AF: 0.594 AC: 2059 AN: 3476

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Calcium oxalate urolithiasis Other:1

association, no assertion criteria provided

case-control

Division of Molecular Genetics and Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University

Mar 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
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: rs7116432; hg19: chr11-35244058; COSMIC: COSV53530497; COSMIC: COSV53530497;