rs1489711013

Variant names:

• chr11-35139343-C-T
• rs1489711013
• NM_000610.4:c.40C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000610.4(CD44):​c.40C>T​(p.Leu14Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,409,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CD44 NM_000610.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.940

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27287883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.40C>T	p.Leu14Phe	missense_variant	Exon 1 of 18	ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.40C>T	p.Leu14Phe	missense_variant	Exon 1 of 18	1	NM_000610.4	ENSP00000398632.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1409450 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 696052

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000270

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.40C>T (p.L14F) alteration is located in exon 1 (coding exon 1) of the CD44 gene. This alteration results from a C to T substitution at nucleotide position 40, causing the leucine (L) at amino acid position 14 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	.;D;T;.;T;.;.;.;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.077	N
LIST_S2	Uncertain	0.89	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L;L;.;L;.;L;.;L;L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.4	D;D;D;D;.;D;.;D;D;D
REVEL	Benign	0.032
Sift	Uncertain	0.0060	D;D;D;D;.;D;.;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;.;D;D;D
Polyphen		0.079	B;D;.;D;.;P;.;.;B;.
Vest4		0.16
MutPred		0.49		Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);Loss of glycosylation at S18 (P = 0.1995);
MVP		0.53
MPC		0.82
ClinPred		0.91	D
GERP RS		-0.012
Varity_R		0.15
gMVP		0.77

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: rs1489711013; hg19: chr11-35160890;