dbSNP rs4445669: CADM1:c.*1957A>G (chr11-115174517-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001301043.2(CADM1):c.*1957A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 984,800 control chromosomes in the GnomAD database, including 144,579 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 0.47 ( 17415 hom., cov: 30)

Exomes 𝑓: 0.55 ( 127164 hom. )

Consequence

CADM1
NM_001301043.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.242

Publications

23 publications found

Variant links:

Genes affected

CADM1 (HGNC:5951): (cell adhesion molecule 1) Enables signaling receptor binding activity. Involved in several processes, including cell recognition; positive regulation of cytokine production; and susceptibility to natural killer cell mediated cytotoxicity. Located in plasma membrane. Implicated in breast carcinoma and prostate cancer. Biomarker of cervix uteri carcinoma in situ. [provided by Alliance of Genome Resources, Apr 2022]

CADM1 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CADM1 links:

Genome browser will be placed here

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=-0.47).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2 link	c.*1957A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11 link	c.*1957A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70718

AN:

151678

Hom.:

17416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.485

GnomAD4 exome

AF:

0.551

AC:

458590

AN:

833004

Hom.:

127164

Cov.:

AF XY:

0.551

AC XY:

211806

AN XY:

384714

show subpopulations

African (AFR)

AF:

0.336

AC:

5301

AN:

15780

American (AMR)

AF:

0.428

AC:

421

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

2613

AN:

5148

East Asian (EAS)

AF:

0.211

AC:

764

AN:

3628

South Asian (SAS)

AF:

0.416

AC:

6848

AN:

16446

European-Finnish (FIN)

AF:

0.533

AC:

375

AN:

704

Middle Eastern (MID)

AF:

0.451

AC:

731

AN:

1620

European-Non Finnish (NFE)

AF:

0.562

AC:

427688

AN:

761412

Other (OTH)

AF:

0.508

AC:

13849

AN:

27282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

10310

20619

30929

41238

51548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16234

32468

48702

64936

81170

<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:

0.466

AC:

70729

AN:

151796

Hom.:

17415

Cov.:

AF XY:

0.462

AC XY:

34287

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.351

AC:

14555

AN:

41412

American (AMR)

AF:

0.421

AC:

6424

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

1759

AN:

3468

East Asian (EAS)

AF:

0.205

AC:

1055

AN:

5152

South Asian (SAS)

AF:

0.411

AC:

1972

AN:

4800

European-Finnish (FIN)

AF:

0.533

AC:

5581

AN:

10470

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.556

AC:

37748

AN:

67922

Other (OTH)

AF:

0.480

AC:

1010

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1812

3624

5436

7248

9060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.521

Hom.:

61859

Bravo

AF:

0.453

Asia WGS

AF:

0.287

AC:

1000

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.24

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