11-35219682-T-C

Variant names:

• chr11-35219682-T-C
• rs2295756
• NM_000610.4:c.1945+295T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000610.4(CD44):​c.1945+295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,136 control chromosomes in the GnomAD database, including 8,920 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 0.33 (8920 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.1945+295T>C		intron_variant	Intron 16 of 17	ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.1945+295T>C		intron_variant	Intron 16 of 17	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50459 AN: 152018 Hom.: 8923 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.332 AC: 50449 AN: 152136 Hom.: 8920 Cov.: 32 AF XY: 0.338 AC XY: 25127 AN XY: 74364

African (AFR) AF: 0.232 AC: 9617 AN: 41502

American (AMR) AF: 0.325 AC: 4961 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3061 AN: 5178

South Asian (SAS) AF: 0.519 AC: 2504 AN: 4826

European-Finnish (FIN) AF: 0.327 AC: 3457 AN: 10584

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24204 AN: 67972

Other (OTH) AF: 0.330 AC: 697 AN: 2112

Alfa AF: 0.354 Hom.: 41819

Bravo AF: 0.324

Asia WGS AF: 0.484 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		0.32
PromoterAI		0.030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2295756; hg19: chr11-35241229;