Genetic Variant CD44:c.68-5908G>A (chr11-35170667-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000610.4(CD44):c.68-5908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,170 control chromosomes in the GnomAD database, including 1,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.16 ( 1980 hom., cov: 33)

Consequence

CD44
NM_000610.4 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.388

Publications

4 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=-0.7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 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	Effect	Exon Rank	Protein
CD44	NM_000610.4	MANE Select	c.68-5908G>A	intron	N/A	NP_000601.3
CD44	NM_001440324.1		c.68-5908G>A	intron	N/A	NP_001427253.1
CD44	NM_001440325.1		c.68-5908G>A	intron	N/A	NP_001427254.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD44	ENST00000428726.8	TSL:1 MANE Select	c.68-5908G>A	intron	N/A	ENSP00000398632.2	P16070-1
CD44	ENST00000415148.6	TSL:1	c.68-5908G>A	intron	N/A	ENSP00000389830.2	P16070-4
CD44	ENST00000433892.6	TSL:1	c.68-5908G>A	intron	N/A	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24501

AN:

152052

Hom.:

1971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.146

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.161

AC:

24535

AN:

152170

Hom.:

1980

Cov.:

AF XY:

0.161

AC XY:

11998

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.182

AC:

7570

AN:

41520

American (AMR)

AF:

0.122

AC:

1868

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

418

AN:

3464

East Asian (EAS)

AF:

0.105

AC:

544

AN:

5186

South Asian (SAS)

AF:

0.239

AC:

1153

AN:

4820

European-Finnish (FIN)

AF:

0.150

AC:

1588

AN:

10584

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10845

AN:

67984

Other (OTH)

AF:

0.144

AC:

305

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1059

2119

3178

4238

5297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.159

Hom.:

853

Bravo

AF:

0.156

Asia WGS

AF:

0.166

AC:

574

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:association

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephrolithiasis, calcium oxalate (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.0

(source)

DANN

Benign

0.81

PhyloP100

0.39

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over