Genetic Variant NM_001301043.2:c.995-5T>C (chr11-115209662-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001301043.2(CADM1):c.995-5T>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000685 in 1,460,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CADM1
NM_001301043.2 splice_region, intron

Scores

Splicing: ADA: 0.004186

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.20

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 11-115209662-A-G is Benign according to our data. Variant chr11-115209662-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 761544.Status of the report is criteria_provided_single_submitter, 1 stars.

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.995-5T>C	splice_region intron	N/A	NP_001287972.1	Q9BY67-3
CADM1	NM_001301044.2		c.995-5T>C	splice_region intron	N/A	NP_001287973.1	X5DQR8
CADM1	NM_001301045.2		c.994+4946T>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.995-5T>C	splice_region intron	N/A	ENSP00000329797.6	Q9BY67-3
CADM1	ENST00000537058.5	TSL:1	c.995-5T>C	splice_region intron	N/A	ENSP00000439817.1	Q9BY67-4
CADM1	ENST00000536727.5	TSL:1	c.994+4946T>C	intron	N/A	ENSP00000440322.1	X5DQS5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460476

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111610

Other (OTH)

AF:

0.0000166

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

5.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0042

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over