NM_000610.4:c.68-5493C>T

Variant names:

• chr11-35171082-C-T
• rs112762
• NM_000610.4:c.68-5493C>T

Variant summary

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

The NM_000610.4(CD44):​c.68-5493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,048 control chromosomes in the GnomAD database, including 24,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.56 (24487 hom., cov: 33)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.163
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.68-5493C>T		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.68-5493C>T		intron_variant	Intron 1 of 17	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84564 AN: 151930 Hom.: 24435 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.557 AC: 84686 AN: 152048 Hom.: 24487 Cov.: 33 AF XY: 0.554 AC XY: 41180 AN XY: 74362

African (AFR) AF: 0.698 AC: 28921 AN: 41462

American (AMR) AF: 0.588 AC: 8985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1791 AN: 3466

East Asian (EAS) AF: 0.307 AC: 1591 AN: 5174

South Asian (SAS) AF: 0.538 AC: 2592 AN: 4818

European-Finnish (FIN) AF: 0.440 AC: 4647 AN: 10566

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

European-Non Finnish (NFE) AF: 0.505 AC: 34324 AN: 67958

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

Alfa AF: 0.448 Hom.: 1805

Bravo AF: 0.570

Asia WGS AF: 0.465 AC: 1616 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	-0.88
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.16
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: rs112762; hg19: chr11-35192629;