11-35150575-G-A

Variant names:

• chr11-35150575-G-A
• rs353623
• NM_000610.4:c.67+11205G>A

Variant summary

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

The NM_000610.4(CD44):​c.67+11205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,086 control chromosomes in the GnomAD database, including 7,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.31 (7793 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.00800
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.67+11205G>A		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.67+11205G>A		intron_variant	Intron 1 of 17	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47755 AN: 151968 Hom.: 7769 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.314 AC: 47808 AN: 152086 Hom.: 7793 Cov.: 32 AF XY: 0.311 AC XY: 23111 AN XY: 74328

African (AFR) AF: 0.396 AC: 16440 AN: 41472

American (AMR) AF: 0.250 AC: 3822 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 824 AN: 3472

East Asian (EAS) AF: 0.105 AC: 545 AN: 5176

South Asian (SAS) AF: 0.250 AC: 1206 AN: 4824

European-Finnish (FIN) AF: 0.304 AC: 3213 AN: 10574

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20734 AN: 67974

Other (OTH) AF: 0.309 AC: 652 AN: 2110

Alfa AF: 0.214 Hom.: 643

Bravo AF: 0.314

Asia WGS AF: 0.216 AC: 753 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Calcium oxalate urolithiasis Other:1

Mar 01, 2014

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

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.69
PhyloP100		-0.0080
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: rs353623; hg19: chr11-35172122;