Genetic Variant CD44:c.*649C>T (chr11-35223027-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000442151.6(CD44):c.*649C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 984,292 control chromosomes in the GnomAD database, including 40,828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5520 hom., cov: 32)

Exomes 𝑓: 0.29 ( 35308 hom. )

Consequence

CD44
ENST00000442151.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.822

Publications

13 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4 link	c.2024+1295C>T		intron_variant	Intron 17 of 17	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.2024+1295C>T		intron_variant	Intron 17 of 17	1	NM_000610.4	ENSP00000398632.2		P16070-1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37200

AN:

151970

Hom.:

5524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0785

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.256

GnomAD4 exome

AF:

0.289

AC:

240176

AN:

832206

Hom.:

35308

Cov.:

AF XY:

0.290

AC XY:

111337

AN XY:

384288

show subpopulations

African (AFR)

AF:

0.0566

AC:

894

AN:

15782

American (AMR)

AF:

0.289

AC:

284

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1737

AN:

5150

East Asian (EAS)

AF:

0.350

AC:

1267

AN:

3620

South Asian (SAS)

AF:

0.466

AC:

7660

AN:

16438

European-Finnish (FIN)

AF:

0.297

AC:

AN:

276

Middle Eastern (MID)

AF:

0.291

AC:

469

AN:

1614

European-Non Finnish (NFE)

AF:

0.289

AC:

219633

AN:

761072

Other (OTH)

AF:

0.299

AC:

8150

AN:

27270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

8374

16748

25122

33496

41870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10026

20052

30078

40104

50130

<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:

0.245

AC:

37202

AN:

152086

Hom.:

5520

Cov.:

AF XY:

0.251

AC XY:

18675

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0786

AC:

3263

AN:

41530

American (AMR)

AF:

0.269

AC:

4115

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1177

AN:

3470

East Asian (EAS)

AF:

0.358

AC:

1851

AN:

5168

South Asian (SAS)

AF:

0.491

AC:

2361

AN:

4810

European-Finnish (FIN)

AF:

0.300

AC:

3164

AN:

10554

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20334

AN:

67970

Other (OTH)

AF:

0.255

AC:

538

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1355

2710

4064

5419

6774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.274

Hom.:

13905

Bravo

AF:

0.232

Asia WGS

AF:

0.364

AC:

1264

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.36

PhyloP100

-0.82

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over