11-35231725-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.*2392C>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 0.342 in 152,050 control chromosomes in the GnomAD database, including 11,469 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 0.34 (11469 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CD44 NM_000610.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD44	NM_000610.4	c.*2392C>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.*2392C>T		3_prime_UTR_variant	18/18	1	NM_000610.4	A2
CD44	ENST00000263398.11	c.*2392C>T		3_prime_UTR_variant	9/9	1		A2

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51882 AN: 151932 Hom.: 11449 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.342 AC: 51952 AN: 152050 Hom.: 11469 Cov.: 32 AF XY: 0.339 AC XY: 25169 AN XY: 74344

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.313

Alfa AF: 0.224 Hom.: 6169

Bravo AF: 0.365

Asia WGS AF: 0.254 AC: 883 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.084
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13347; hg19: chr11-35253272;