rs3794110

Variant names:

• chr11-35170667-G-A
• rs3794110
• NM_000610.4:c.68-5908G>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.68-5908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,170 control chromosomes in the GnomAD database, including 1,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.16 (1980 hom., cov: 33)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.388
• 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.68-5908G>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.68-5908G>A		intron_variant	Intron 1 of 17	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24501 AN: 152052 Hom.: 1971 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.161 AC: 24535 AN: 152170 Hom.: 1980 Cov.: 33 AF XY: 0.161 AC XY: 11998 AN XY: 74406

African (AFR) AF: 0.182 AC: 7570 AN: 41520

American (AMR) AF: 0.122 AC: 1868 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3464

East Asian (EAS) AF: 0.105 AC: 544 AN: 5186

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4820

European-Finnish (FIN) AF: 0.150 AC: 1588 AN: 10584

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10845 AN: 67984

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.159 Hom.: 853

Bravo AF: 0.156

Asia WGS AF: 0.166 AC: 574 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	-0.70
CADD	Benign	7.0
DANN	Benign	0.81
PhyloP100		0.39
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: rs3794110; hg19: chr11-35192214;