rs996076

Positions:

• chr11-35189251-G-A
• chr11-35189251-G-C

Variant summary

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

The NM_000610.4(CD44):​c.437-584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,028 control chromosomes in the GnomAD database, including 21,773 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 0.53 (21773 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD44	NM_000610.4	c.437-584G>A		intron_variant		ENST00000428726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD44	ENST00000428726.8	c.437-584G>A		intron_variant		1	NM_000610.4	A2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80149 AN: 151910 Hom.: 21778 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.527 AC: 80158 AN: 152028 Hom.: 21773 Cov.: 32 AF XY: 0.537 AC XY: 39943 AN XY: 74322

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.518

Alfa AF: 0.535 Hom.: 28909

Bravo AF: 0.505

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.69
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs996076; hg19: chr11-35210798;