11-35163183-G-T

Position:

• chr11-35163183-G-T

Variant summary

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

The NM_000610.4(CD44):​c.68-13392G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,996 control chromosomes in the GnomAD database, including 6,540 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 0.28 (6540 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552

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 = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD44	NM_000610.4	c.68-13392G>T		intron_variant		ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.68-13392G>T		intron_variant		1	NM_000610.4	ENSP00000398632	A2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43135 AN: 151882 Hom.: 6507 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.284 AC: 43221 AN: 151996 Hom.: 6540 Cov.: 32 AF XY: 0.285 AC XY: 21194 AN XY: 74292

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.273

Alfa AF: 0.266 Hom.: 718

Bravo AF: 0.288

Asia WGS AF: 0.217 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.45

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: rs353636; hg19: chr11-35184730;