11-115214681-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001301043.2(CADM1):c.921T>C(p.Asp307=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,614,050 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (13 hom.)
• Consequence: CADM1 NM_001301043.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.27

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 11-115214681-A-G is Benign according to our data. Variant chr11-115214681-A-G is described in ClinVar as [Benign]. Clinvar id is 719362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.27 with no splicing effect.
• BS2: High AC in GnomAd at 334 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM1	NM_001301043.2	c.921T>C	p.Asp307=	synonymous_variant	7/12	ENST00000331581.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM1	ENST00000331581.11	c.921T>C	p.Asp307=	synonymous_variant	7/12	1	NM_001301043.2	P4

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 334 AN: 152156 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00220 AC: 551 AN: 250994 Hom.: 5 AF XY: 0.00239 AC XY: 324 AN XY: 135624

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000817

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00281

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00240 AC: 3514 AN: 1461776 Hom.: 13 Cov.: 31 AF XY: 0.00240 AC XY: 1742 AN XY: 727194

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.0129

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000962

Gnomad4 FIN exome AF: 0.00139

Gnomad4 NFE exome AF: 0.00246

Gnomad4 OTH exome AF: 0.00316

GnomAD4 genome AF: 0.00219 AC: 334 AN: 152274 Hom.: 1 Cov.: 32 AF XY: 0.00212 AC XY: 158 AN XY: 74452

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00316

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00300 Hom.: 1

Bravo AF: 0.00210

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00327

EpiControl AF: 0.00522

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	-0.49
Cadd	Benign	7.6
Dann	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs139604912; hg19: chr11-115085401; COSMIC: COSV59024447; COSMIC: COSV59024447;