NM_000610.4:c.68-2181G>C

Variant names:

• chr11-35174394-G-C
• rs11033013
• NM_000610.4:c.68-2181G>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.68-2181G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,100 control chromosomes in the GnomAD database, including 5,415 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 0.26 (5415 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.68-2181G>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.68-2181G>C		intron_variant	Intron 1 of 17	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39813 AN: 151982 Hom.: 5399 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0804

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.262 AC: 39881 AN: 152100 Hom.: 5415 Cov.: 32 AF XY: 0.260 AC XY: 19305 AN XY: 74364

African (AFR) AF: 0.301 AC: 12487 AN: 41482

American (AMR) AF: 0.269 AC: 4118 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3470

East Asian (EAS) AF: 0.0808 AC: 418 AN: 5172

South Asian (SAS) AF: 0.165 AC: 798 AN: 4822

European-Finnish (FIN) AF: 0.214 AC: 2270 AN: 10588

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17784 AN: 67958

Other (OTH) AF: 0.266 AC: 563 AN: 2114

Alfa AF: 0.133 Hom.: 223

Bravo AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.095
DANN	Benign	0.33
PhyloP100		-2.2
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: rs11033013; hg19: chr11-35195941;