NM_000610.4:c.*2253C>T

Variant names:

• chr11-35231586-C-T
• rs10836347
• NM_000610.4:c.*2253C>T

Variant summary

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

The NM_000610.4(CD44):​c.*2253C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,212 control chromosomes in the GnomAD database, including 984 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 0.11 (984 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD44 NM_000610.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 23 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.*2253C>T		3_prime_UTR_variant	Exon 18 of 18	ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.*2253C>T		3_prime_UTR_variant	Exon 18 of 18	1	NM_000610.4	ENSP00000398632.2
CD44	ENST00000263398.11	c.*2253C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000263398.6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16097 AN: 152096 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.119

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.106 AC: 16129 AN: 152212 Hom.: 984 Cov.: 32 AF XY: 0.107 AC XY: 7931 AN XY: 74432

African (AFR) AF: 0.0446 AC: 1852 AN: 41546

American (AMR) AF: 0.171 AC: 2611 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3468

East Asian (EAS) AF: 0.0871 AC: 451 AN: 5180

South Asian (SAS) AF: 0.0684 AC: 330 AN: 4828

European-Finnish (FIN) AF: 0.132 AC: 1399 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8682 AN: 67992

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.115 Hom.: 1631

Bravo AF: 0.106

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10836347; hg19: chr11-35253133;