rs353630

chr11-35166644-G-A

Variant summary

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

The NM_000610.4(CD44):c.68-9931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,058 control chromosomes in the GnomAD database, including 8,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.32 (8761 hom., cov: 33)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.408

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD44	NM_000610.4	c.68-9931G>A		intron_variant		ENST00000428726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD44	ENST00000428726.8	c.68-9931G>A		intron_variant		1	NM_000610.4	A2

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49234 AN: 151940 Hom.: 8738 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.324 AC: 49312 AN: 152058 Hom.: 8761 Cov.: 33 AF XY: 0.325 AC XY: 24143 AN XY: 74338

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0369

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.318

Alfa AF: 0.278 Hom.: 8763

Bravo AF: 0.328

Asia WGS AF: 0.203 AC: 709 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephrolithiasis, calcium oxalate 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.0
Dann	Benign	0.58

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: rs353630; hg19: chr11-35188191;