Genetic Variant CADM1:c.722-2408A>C (chr11-115220399-T-G) – 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.722-2408A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,192 control chromosomes in the GnomAD database, including 3,827 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 0.20 ( 3827 hom., cov: 32)

Consequence

CADM1
NM_001301043.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.316

Publications

12 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

new If you want to explore the variant's impact on the transcript NM_001301043.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301043.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CADM1	NM_001301043.2	MANE Select	c.722-2408A>C	intron	N/A	NP_001287972.1	Q9BY67-3
CADM1	NM_001301044.2		c.722-2408A>C	intron	N/A	NP_001287973.1	X5DQR8
CADM1	NM_001301045.2		c.722-2408A>C	intron	N/A	NP_001287974.1	X5DQS5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CADM1	ENST00000331581.11	TSL:1 MANE Select	c.722-2408A>C	intron	N/A	ENSP00000329797.6	Q9BY67-3
CADM1	ENST00000537058.5	TSL:1	c.722-2408A>C	intron	N/A	ENSP00000439817.1	Q9BY67-4
CADM1	ENST00000536727.5	TSL:1	c.722-2408A>C	intron	N/A	ENSP00000440322.1	X5DQS5

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30671

AN:

152074

Hom.:

3821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0642

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.192

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

GnomAD4 genome

AF:

0.202

AC:

30684

AN:

152192

Hom.:

3827

Cov.:

AF XY:

0.203

AC XY:

15103

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0642

AC:

2666

AN:

41548

American (AMR)

AF:

0.248

AC:

3779

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

617

AN:

3472

East Asian (EAS)

AF:

0.111

AC:

576

AN:

5182

South Asian (SAS)

AF:

0.353

AC:

1701

AN:

4814

European-Finnish (FIN)

AF:

0.262

AC:

2781

AN:

10598

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

18022

AN:

67994

Other (OTH)

AF:

0.190

AC:

402

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1209

2418

3626

4835

6044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.234

Hom.:

1713

Bravo

AF:

0.192

Asia WGS

AF:

0.211

AC:

732

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.0

(source)

DANN

Benign

0.70

PhyloP100

0.32

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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