chr11-115178716-C-T

Variant names:

• chr11-115178716-C-T
• rs867859915
• NM_001301043.2:c.1225G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001301043.2(CADM1):​c.1225G>A​(p.Val409Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V409V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CADM1 NM_001301043.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31522226).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	NM_001301043.2	MANE Select	c.1225G>A	p.Val409Ile	missense	Exon 11 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.1171G>A	p.Val391Ile	missense	Exon 10 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_001301045.2		c.1141G>A	p.Val381Ile	missense	Exon 10 of 11	NP_001287974.1	X5DQS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	ENST00000331581.11	TSL:1 MANE Select	c.1225G>A	p.Val409Ile	missense	Exon 11 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.1171G>A	p.Val391Ile	missense	Exon 10 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000536727.5	TSL:1	c.1141G>A	p.Val381Ile	missense	Exon 10 of 11	ENSP00000440322.1	X5DQS5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251234 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461614 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 727116

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53208

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111952

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.38	T
Polyphen		0.94	P
Vest4		0.43
MutPred		0.50		Gain of sheet (P = 0.0477)
MVP		0.58
MPC		0.89
ClinPred		0.35	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.55
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs867859915; hg19: chr11-115049436;