Genetic Variant NM_000610.4:c.1683C>T (chr11-35211322-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000610.4(CD44):c.1683C>T(p.Thr561Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,613,876 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

CD44
NM_000610.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.379

Publications

1 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:

CD44-AS1 (HGNC:40133): (CD44 antisense RNA 1)

CD44-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-35211322-C-T is Benign according to our data. Variant chr11-35211322-C-T is described in ClinVar as Benign. ClinVar VariationId is 782773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.379 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 BG gene

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.1683C>T	p.Thr561Thr	synonymous	Exon 14 of 18	NP_000601.3
CD44	NM_001440324.1		c.1686C>T	p.Thr562Thr	synonymous	Exon 14 of 18	NP_001427253.1
CD44	NM_001440325.1		c.1680C>T	p.Thr560Thr	synonymous	Exon 14 of 18	NP_001427254.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD44	ENST00000428726.8	TSL:1 MANE Select	c.1683C>T	p.Thr561Thr	synonymous	Exon 14 of 18	ENSP00000398632.2	P16070-1
CD44	ENST00000415148.6	TSL:1	c.1554C>T	p.Thr518Thr	synonymous	Exon 13 of 17	ENSP00000389830.2	P16070-4
CD44	ENST00000433892.6	TSL:1	c.936C>T	p.Thr312Thr	synonymous	Exon 8 of 12	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

189

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00163

AC:

410

AN:

251090

AF XY:

0.00175

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00151

AC:

2208

AN:

1461588

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1143

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33472

American (AMR)

AF:

0.00163

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00176

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.00147

AC:

127

AN:

86256

European-Finnish (FIN)

AF:

0.000393

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00159

AC:

1764

AN:

1111762

Other (OTH)

AF:

0.00197

AC:

119

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

119

238

356

475

594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.00124

AC:

189

AN:

152288

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41558

American (AMR)

AF:

0.00118

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00187

AC:

127

AN:

68020

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00172

Hom.:

Bravo

AF:

0.00131

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00219

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.40

(source)

DANN

Benign

0.25

PhyloP100

-0.38

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over