11-115217903-G-C

Variant names:

• chr11-115217903-G-C
• rs770714520
• NM_001301043.2:c.810C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001301043.2(CADM1):​c.810C>G​(p.Ile270Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CADM1 NM_001301043.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2974829).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.810C>G	p.Ile270Met	missense_variant	Exon 6 of 12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.810C>G	p.Ile270Met	missense_variant	Exon 6 of 12	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T;.;.;.;T;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.30	T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.80	N;.;N;N;.;N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.40	N;.;N;N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.21	T;.;T;T;T;T;.
Sift4G	Benign	0.21	T;T;T;T;T;T;T
Polyphen		0.45	B;.;.;.;.;.;.
Vest4		0.36
MutPred		0.42		Gain of ubiquitination at K272 (P = 0.0525);.;Gain of ubiquitination at K272 (P = 0.0525);Gain of ubiquitination at K272 (P = 0.0525);Gain of ubiquitination at K272 (P = 0.0525);Gain of ubiquitination at K272 (P = 0.0525);.;
MVP		0.68
MPC		1.5
ClinPred		0.70	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs770714520; hg19: chr11-115088623;