rs10836347

chr11-35231586-C-T

Variant summary

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

The NM_000610.4(CD44):c.*2253C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,212 control chromosomes in the GnomAD database, including 984 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 0.11 (984 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD44 NM_000610.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD44	NM_000610.4	c.*2253C>T		3_prime_UTR_variant	18/18	ENST00000428726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD44	ENST00000428726.8	c.*2253C>T		3_prime_UTR_variant	18/18	1	NM_000610.4	A2
CD44	ENST00000263398.11	c.*2253C>T		3_prime_UTR_variant	9/9	1		A2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16097 AN: 152096 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.119

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.106 AC: 16129 AN: 152212 Hom.: 984 Cov.: 32 AF XY: 0.107 AC XY: 7931 AN XY: 74432

Gnomad4 AFR AF: 0.0446

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0871

Gnomad4 SAS AF: 0.0684

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.127

Alfa AF: 0.122 Hom.: 1108

Bravo AF: 0.106

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.0
Dann	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10836347; hg19: chr11-35253133;