11-115229275-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001301043.2(CADM1):c.563-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,613,914 control chromosomes in the GnomAD database, including 82 homozygotes. 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (32 hom.)
• Consequence: CADM1 NM_001301043.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003252
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.373

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-115229275-G-A is Benign according to our data. Variant chr11-115229275-G-A is described in ClinVar as [Benign]. Clinvar id is 776661.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1913/152260) while in subpopulation AFR AF= 0.0435 (1808/41546). AF 95% confidence interval is 0.0418. There are 50 homozygotes in gnomad4. There are 907 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1908 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM1	NM_001301043.2	c.563-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000331581.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM1	ENST00000331581.11	c.563-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001301043.2	P4

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1908 AN: 152142 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00338 AC: 848 AN: 251178 Hom.: 16 AF XY: 0.00246 AC XY: 334 AN XY: 135750

Gnomad AFR exome AF: 0.0448

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00143 AC: 2093 AN: 1461654 Hom.: 32 Cov.: 31 AF XY: 0.00126 AC XY: 916 AN XY: 727142

Gnomad4 AFR exome AF: 0.0463

Gnomad4 AMR exome AF: 0.00275

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000188

Gnomad4 OTH exome AF: 0.00325

GnomAD4 genome AF: 0.0126 AC: 1913 AN: 152260 Hom.: 50 Cov.: 33 AF XY: 0.0122 AC XY: 907 AN XY: 74444

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00646 Hom.: 5

Bravo AF: 0.0147

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.86
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000033
dbscSNV1_RF	Benign	0.0
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

LitVar

Other links and lift over

dbSNP: rs12276946; hg19: chr11-115099995; COSMIC: COSV104404149; COSMIC: COSV104404149;