NM_000610.4:c.1250A>G

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.1250A>G(p.Lys417Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,611,714 control chromosomes in the GnomAD database, including 410,458 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 0.76 ( 44325 hom., cov: 32)

Exomes 𝑓: 0.70 ( 366133 hom. )

Consequence

CD44
NM_000610.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.466

Publications

54 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=7.028172E-7).

BP6

Variant 11-35204608-A-G is Benign according to our data. Variant chr11-35204608-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059515.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD44	NM_000610.4	MANE Select	c.1250A>G	p.Lys417Arg	missense	Exon 10 of 18	NP_000601.3
CD44	NM_001440324.1		c.1253A>G	p.Lys418Arg	missense	Exon 10 of 18	NP_001427253.1
CD44	NM_001440325.1		c.1250A>G	p.Lys417Arg	missense	Exon 10 of 18	NP_001427254.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD44	ENST00000428726.8	TSL:1 MANE Select	c.1250A>G	p.Lys417Arg	missense	Exon 10 of 18	ENSP00000398632.2
CD44	ENST00000415148.6	TSL:1	c.1121A>G	p.Lys374Arg	missense	Exon 9 of 17	ENSP00000389830.2
CD44	ENST00000433892.6	TSL:1	c.668-3497A>G		intron	N/A	ENSP00000392331.2

Frequencies

GnomAD3 genomes

AF:

0.758

AC:

115177

AN:

152030

Hom.:

44275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.879

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.776

Gnomad EAS

AF:

0.928

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.744

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.749

GnomAD2 exomes

AF:

0.741

AC:

186203

AN:

251120

AF XY:

0.741

show subpopulations

Gnomad AFR exome

AF:

0.881

Gnomad AMR exome

AF:

0.682

Gnomad ASJ exome

AF:

0.769

Gnomad EAS exome

AF:

0.926

Gnomad FIN exome

AF:

0.734

Gnomad NFE exome

AF:

0.689

Gnomad OTH exome

AF:

0.726

GnomAD4 exome

AF:

0.705

AC:

1028972

AN:

1459564

Hom.:

366133

Cov.:

AF XY:

0.708

AC XY:

514030

AN XY:

726236

show subpopulations

African (AFR)

AF:

0.882

AC:

29493

AN:

33420

American (AMR)

AF:

0.685

AC:

30596

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.767

AC:

20018

AN:

26090

East Asian (EAS)

AF:

0.943

AC:

37391

AN:

39670

South Asian (SAS)

AF:

0.821

AC:

70775

AN:

86218

European-Finnish (FIN)

AF:

0.730

AC:

38963

AN:

53396

Middle Eastern (MID)

AF:

0.712

AC:

4102

AN:

5758

European-Non Finnish (NFE)

AF:

0.679

AC:

754252

AN:

1110034

Other (OTH)

AF:

0.719

AC:

43382

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

13401

26803

40204

53606

67007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19476

38952

58428

77904

97380

<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:

0.758

AC:

115284

AN:

152150

Hom.:

44325

Cov.:

AF XY:

0.764

AC XY:

56834

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.879

AC:

36513

AN:

41528

American (AMR)

AF:

0.703

AC:

10744

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

2696

AN:

3472

East Asian (EAS)

AF:

0.928

AC:

4802

AN:

5176

South Asian (SAS)

AF:

0.825

AC:

3973

AN:

4816

European-Finnish (FIN)

AF:

0.744

AC:

7873

AN:

10578

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.681

AC:

46284

AN:

67974

Other (OTH)

AF:

0.751

AC:

1589

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1375

2751

4126

5502

6877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.715

Hom.:

104117

Bravo

AF:

0.760

TwinsUK

AF:

0.690

AC:

2559

ALSPAC

AF:

0.674

AC:

2597

ESP6500AA

AF:

0.867

AC:

3820

ESP6500EA

AF:

0.693

AC:

5961

ExAC

AF:

0.748

AC:

90765

Asia WGS

AF:

0.874

AC:

3039

AN:

3478

EpiCase

AF:

0.684

EpiControl

AF:

0.682

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.1

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.23

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.22

MetaRNN

Benign

7.0e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.23

PhyloP100

0.47

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.030

REVEL

Benign

0.028

Sift

Benign

0.89

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.0080

MPC

0.038

ClinPred

0.00040

GERP RS

1.9

Varity_R

0.026

gMVP

0.066

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over