rs187115

Variant names:

• chr11-35154612-T-C
• rs187115
• NM_000610.4:c.67+15242T>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.67+15242T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,062 control chromosomes in the GnomAD database, including 10,697 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 0.37 (10697 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67
• Publications: 51 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.67+15242T>C		intron_variant	Intron 1 of 17	ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.67+15242T>C		intron_variant	Intron 1 of 17	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56217 AN: 151944 Hom.: 10666 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.370 AC: 56289 AN: 152062 Hom.: 10697 Cov.: 32 AF XY: 0.368 AC XY: 27323 AN XY: 74342

African (AFR) AF: 0.456 AC: 18908 AN: 41454

American (AMR) AF: 0.368 AC: 5618 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1170 AN: 3460

East Asian (EAS) AF: 0.196 AC: 1016 AN: 5184

South Asian (SAS) AF: 0.305 AC: 1467 AN: 4816

European-Finnish (FIN) AF: 0.322 AC: 3413 AN: 10590

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23496 AN: 67968

Other (OTH) AF: 0.376 AC: 792 AN: 2108

Alfa AF: 0.367 Hom.: 8740

Bravo AF: 0.376

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.50
PhyloP100		-2.7
Mutation Taster		=98/2	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: rs187115; hg19: chr11-35176159;