rs8193

Positions:

• chr11-35229771-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.*438C>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 0.302 in 175,070 control chromosomes in the GnomAD database, including 9,503 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 0.30 (7971 hom., cov: 32)
  • Exomes 𝑓: 0.35 (1532 hom.)
• Consequence: CD44 NM_000610.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD44	NM_000610.4	c.*438C>T		3_prime_UTR_variant	18/18	ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.*438C>T		3_prime_UTR_variant	18/18	1	NM_000610.4	ENSP00000398632	A2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44895 AN: 151968 Hom.: 7974 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.348 AC: 7992 AN: 22984 Hom.: 1532 Cov.: 0 AF XY: 0.354 AC XY: 4277 AN XY: 12080

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.295 AC: 44892 AN: 152086 Hom.: 7971 Cov.: 32 AF XY: 0.303 AC XY: 22498 AN XY: 74334

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.322

Alfa AF: 0.354 Hom.: 14042

Bravo AF: 0.283

Asia WGS AF: 0.450 AC: 1562 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs8193; hg19: chr11-35251318;