rs353639

Variant names:

• chr11-35162817-T-G
• rs353639
• NM_000610.4:c.68-13758T>G

Variant summary

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

The NM_000610.4(CD44):​c.68-13758T>G 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 151,762 control chromosomes in the GnomAD database, including 8,527 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8527 hom., cov: 31)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 16 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]

SNORD164 (HGNC:51878): (small nucleolar RNA, C/D box 164)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.68-13758T>G		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.68-13758T>G		intron_variant	Intron 1 of 17	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47570 AN: 151644 Hom.: 8488 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.314 AC: 47667 AN: 151762 Hom.: 8527 Cov.: 31 AF XY: 0.314 AC XY: 23275 AN XY: 74158

African (AFR) AF: 0.496 AC: 20468 AN: 41304

American (AMR) AF: 0.282 AC: 4297 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 560 AN: 3464

East Asian (EAS) AF: 0.121 AC: 625 AN: 5162

South Asian (SAS) AF: 0.238 AC: 1149 AN: 4828

European-Finnish (FIN) AF: 0.300 AC: 3155 AN: 10506

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16500 AN: 67942

Other (OTH) AF: 0.292 AC: 615 AN: 2104

Alfa AF: 0.272 Hom.: 12027

Bravo AF: 0.322

Asia WGS AF: 0.227 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.55
PhyloP100		-1.2
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: rs353639; hg19: chr11-35184364;