Genetic Variant CADM1:p.Thr346_Thr353dup (chr11-115209591-A-ATGGTGGTGGTGGTGGTGGTGGTGG) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001301043.2(CADM1):c.1037_1060dupCCACCACCACCACCACCACCACCA(p.Thr346_Thr353dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 785,848 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

CADM1
NM_001301043.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001301043.2

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	HGVSp	Effect	Exon Rank	Protein	UniProt
CADM1	NM_001301043.2	MANE Select	c.1037_1060dupCCACCACCACCACCACCACCACCA	p.Thr346_Thr353dup	conservative_inframe_insertion	Exon 8 of 12	NP_001287972.1	Q9BY67-3
CADM1	NM_001301044.2		c.1037_1060dupCCACCACCACCACCACCACCACCA	p.Thr346_Thr353dup	conservative_inframe_insertion	Exon 8 of 11	NP_001287973.1	X5DQR8
CADM1	NM_014333.4		c.1037_1060dupCCACCACCACCACCACCACCACCA	p.Thr346_Thr353dup	conservative_inframe_insertion	Exon 8 of 10	NP_055148.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CADM1	ENST00000331581.11	TSL:1 MANE Select	c.1037_1060dupCCACCACCACCACCACCACCACCA	p.Thr346_Thr353dup	conservative_inframe_insertion	Exon 8 of 12	ENSP00000329797.6	Q9BY67-3
CADM1	ENST00000537058.5	TSL:1	c.1037_1060dupCCACCACCACCACCACCACCACCA	p.Thr346_Thr353dup	conservative_inframe_insertion	Exon 8 of 11	ENSP00000439817.1	Q9BY67-4
CADM1	ENST00000452722.7	TSL:1	c.1037_1060dupCCACCACCACCACCACCACCACCA	p.Thr346_Thr353dup	conservative_inframe_insertion	Exon 8 of 10	ENSP00000395359.2	Q9BY67-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000127

AC:

AN:

785848

Hom.:

Cov.:

AF XY:

0.00000244

AC XY:

AN XY:

409314

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

20070

American (AMR)

AF:

0.00

AC:

AN:

39932

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17920

East Asian (EAS)

AF:

0.00

AC:

AN:

25552

South Asian (SAS)

AF:

0.00

AC:

AN:

72320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3922

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

531724

Other (OTH)

AF:

0.00

AC:

AN:

34038

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over