Variant 11-35204608-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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 criteria provided, single submitter B:1

Conservation

PhyloP100: 0.466

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD44	NM_000610.4 linkuse as main transcript	c.1250A>G	p.Lys417Arg	missense_variant	10/18	ENST00000428726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD44	ENST00000428726.8 linkuse as main transcript	c.1250A>G	p.Lys417Arg	missense_variant	10/18	1	NM_000610.4	A2	P16070-1

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

GnomAD3 exomes

AF:

0.741

AC:

186203

AN:

251120

Hom.:

69997

AF XY:

0.741

AC XY:

100621

AN XY:

135710

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 SAS exome

AF:

0.820

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

Gnomad4 AFR exome

AF:

0.882

Gnomad4 AMR exome

AF:

0.685

Gnomad4 ASJ exome

AF:

0.767

Gnomad4 EAS exome

AF:

0.943

Gnomad4 SAS exome

AF:

0.821

Gnomad4 FIN exome

AF:

0.730

Gnomad4 NFE exome

AF:

0.679

Gnomad4 OTH exome

AF:

0.719

GnomAD4 genome

AF:

0.758

AC:

115284

AN:

152150

Hom.:

44325

Cov.:

AF XY:

0.764

AC XY:

56834

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.879

Gnomad4 AMR

AF:

0.703

Gnomad4 ASJ

AF:

0.776

Gnomad4 EAS

AF:

0.928

Gnomad4 SAS

AF:

0.825

Gnomad4 FIN

AF:

0.744

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.751

Alfa

AF:

0.703

Hom.:

63440

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: criteria provided, single submitter

LINK: link

Submissions by phenotype

CD44-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

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

0.069

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.1

DANN

Benign

0.58

DEOGEN2

Benign

0.23

T;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.22

T;T;T;T

MetaRNN

Benign

7.0e-7

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.23

N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.030

N;N;N;N

REVEL

Benign

0.028

Sift

Benign

0.89

T;T;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.0080

MPC

0.038

ClinPred

0.00040

GERP RS

1.9

Varity_R

0.026

gMVP

0.066

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over