NM_000610.4:c.1436T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000610.4(CD44):c.1436T>C(p.Ile479Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 1,606,644 control chromosomes in the GnomAD database, including 564,645 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.88 ( 59049 hom., cov: 33)

Exomes 𝑓: 0.83 ( 505596 hom. )

Consequence

CD44
NM_000610.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.13

Publications

73 publications found

Variant links:

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]

CD44 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.0478313E-7).

BP6

Variant 11-35208126-T-C is Benign according to our data. Variant chr11-35208126-T-C is described in ClinVar as Benign. ClinVar VariationId is 3058927.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4 link	c.1436T>C	p.Ile479Thr	missense_variant	Exon 12 of 18	ENST00000428726.8	NP_000601.3	P16070-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8 link	c.1436T>C	p.Ile479Thr	missense_variant	Exon 12 of 18	1	NM_000610.4	ENSP00000398632.2		P16070-1

Frequencies

GnomAD3 genomes

AF:

0.878

AC:

133510

AN:

152142

Hom.:

58984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.966

Gnomad AMI

AF:

0.794

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.917

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.848

Gnomad MID

AF:

0.937

Gnomad NFE

AF:

0.810

Gnomad OTH

AF:

0.875

GnomAD2 exomes

AF:

0.881

AC:

221102

AN:

251076

AF XY:

0.878

show subpopulations

Gnomad AFR exome

AF:

0.968

Gnomad AMR exome

AF:

0.929

Gnomad ASJ exome

AF:

0.914

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.845

Gnomad NFE exome

AF:

0.819

Gnomad OTH exome

AF:

0.873

GnomAD4 exome

AF:

0.831

AC:

1209307

AN:

1454384

Hom.:

505596

Cov.:

AF XY:

0.835

AC XY:

604401

AN XY:

723996

show subpopulations

African (AFR)

AF:

0.971

AC:

32366

AN:

33336

American (AMR)

AF:

0.926

AC:

41374

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.916

AC:

23892

AN:

26076

East Asian (EAS)

AF:

1.00

AC:

39634

AN:

39642

South Asian (SAS)

AF:

0.950

AC:

81773

AN:

86098

European-Finnish (FIN)

AF:

0.842

AC:

44967

AN:

53394

Middle Eastern (MID)

AF:

0.936

AC:

5391

AN:

5758

European-Non Finnish (NFE)

AF:

0.804

AC:

888779

AN:

1105202

Other (OTH)

AF:

0.850

AC:

51131

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

9043

18087

27130

36174

45217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20698

41396

62094

82792

103490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.878

AC:

133633

AN:

152260

Hom.:

59049

Cov.:

AF XY:

0.883

AC XY:

65757

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.967

AC:

40173

AN:

41564

American (AMR)

AF:

0.888

AC:

13572

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.917

AC:

3183

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5184

AN:

5192

South Asian (SAS)

AF:

0.953

AC:

4592

AN:

4820

European-Finnish (FIN)

AF:

0.848

AC:

8980

AN:

10592

Middle Eastern (MID)

AF:

0.932

AC:

274

AN:

294

European-Non Finnish (NFE)

AF:

0.810

AC:

55100

AN:

68010

Other (OTH)

AF:

0.876

AC:

1851

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

826

1652

2477

3303

4129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.839

Hom.:

194148

Bravo

AF:

0.884

TwinsUK

AF:

0.800

AC:

2967

ALSPAC

AF:

0.799

AC:

3080

ESP6500AA

AF:

0.960

AC:

4228

ESP6500EA

AF:

0.814

AC:

6994

ExAC

AF:

0.881

AC:

106921

Asia WGS

AF:

0.975

AC:

3391

AN:

3478

EpiCase

AF:

0.821

EpiControl

AF:

0.822

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CD44-related disorder

Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.22

T;.;.;.;.;T;.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.10

T;T;T;T;T;T;T;T

MetaRNN

Benign

7.0e-7

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.8

N;.;.;.;.;.;.;.

PhyloP100

2.1

PrimateAI

Benign

0.37

PROVEAN

Benign

2.5

N;N;N;.;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;.;T;T;T;T

Sift4G

Benign

1.0

T;T;T;.;T;T;T;T

Polyphen

0.0

B;B;B;.;.;.;.;.

Vest4

0.024

MPC

0.050

ClinPred

0.0078

GERP RS

6.2

Varity_R

0.032

gMVP

0.052

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over