chr11-115217927-C-T

Variant names:

• chr11-115217927-C-T
• rs113893105
• NM_001301043.2:c.786G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001301043.2(CADM1):​c.786G>A​(p.Ala262Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,506 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (11 hom., cov: 32)
  • Exomes 𝑓: 0.011 (127 hom.)
• Consequence: CADM1 NM_001301043.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0380
• Publications: 7 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.085).
• BP6: Variant 11-115217927-C-T is Benign according to our data. Variant chr11-115217927-C-T is described in ClinVar as Benign. ClinVar VariationId is 770982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0109 (15942/1461214) while in subpopulation MID AF = 0.0203 (117/5762). AF 95% confidence interval is 0.0173. There are 127 homozygotes in GnomAdExome4. There are 7975 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1266 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.786G>A	p.Ala262Ala	synonymous	Exon 6 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.786G>A	p.Ala262Ala	synonymous	Exon 6 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_001301045.2		c.786G>A	p.Ala262Ala	synonymous	Exon 6 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.786G>A	p.Ala262Ala	synonymous	Exon 6 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.786G>A	p.Ala262Ala	synonymous	Exon 6 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000536727.5	TSL:1	c.786G>A	p.Ala262Ala	synonymous	Exon 6 of 11	ENSP00000440322.1	X5DQS5

Frequencies

GnomAD3 genomes AF: 0.00825 AC: 1256 AN: 152174 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00764

GnomAD2 exomes AF: 0.00866 AC: 2175 AN: 251204 AF XY: 0.00884

Gnomad AFR exome AF: 0.00289

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00645

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00684

Gnomad NFE exome AF: 0.0149

Gnomad OTH exome AF: 0.00897

GnomAD4 exome AF: 0.0109 AC: 15942 AN: 1461214 Hom.: 127 Cov.: 30 AF XY: 0.0110 AC XY: 7975 AN XY: 726944

African (AFR) AF: 0.00404 AC: 135 AN: 33438

American (AMR) AF: 0.00432 AC: 193 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00498 AC: 130 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00152 AC: 131 AN: 86250

European-Finnish (FIN) AF: 0.00743 AC: 397 AN: 53410

Middle Eastern (MID) AF: 0.0203 AC: 117 AN: 5762

European-Non Finnish (NFE) AF: 0.0128 AC: 14282 AN: 1111510

Other (OTH) AF: 0.00923 AC: 557 AN: 60352

GnomAD4 genome AF: 0.00831 AC: 1266 AN: 152292 Hom.: 11 Cov.: 32 AF XY: 0.00794 AC XY: 591 AN XY: 74462

African (AFR) AF: 0.00342 AC: 142 AN: 41552

American (AMR) AF: 0.00405 AC: 62 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10614

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0140 AC: 951 AN: 68034

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.0106 Hom.: 6

Bravo AF: 0.00773

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0146

EpiControl AF: 0.0148

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		-0.038
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs113893105; hg19: chr11-115088647; COSMIC: COSV100523695; COSMIC: COSV100523695;