chr11-115209591-A-ATGG

Variant names:

• chr11-115209591-A-ATGG
• rs747352768
• NM_001301043.2:c.1058_1060dupCCA

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_001301043.2(CADM1):​c.1058_1060dupCCA​(p.Thr353dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 924,502 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (2 hom.)
• Consequence: CADM1 NM_001301043.2 conservative_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07
• Publications: 3 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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001301043.2
• BP6: Variant 11-115209591-A-ATGG is Benign according to our data. Variant chr11-115209591-A-ATGG is described in ClinVar as Likely_benign. ClinVar VariationId is 776659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00295 (2315/785344) while in subpopulation AFR AF = 0.0199 (400/20052). AF 95% confidence interval is 0.0183. There are 2 homozygotes in GnomAdExome4. There are 1157 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 610 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.1058_1060dupCCA	p.Thr353dup	conservative_inframe_insertion	Exon 8 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.1058_1060dupCCA	p.Thr353dup	conservative_inframe_insertion	Exon 8 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_014333.4		c.1058_1060dupCCA	p.Thr353dup	conservative_inframe_insertion	Exon 8 of 10	NP_055148.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	ENST00000331581.11	TSL:1 MANE Select	c.1058_1060dupCCA	p.Thr353dup	conservative_inframe_insertion	Exon 8 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.1058_1060dupCCA	p.Thr353dup	conservative_inframe_insertion	Exon 8 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000452722.7	TSL:1	c.1058_1060dupCCA	p.Thr353dup	conservative_inframe_insertion	Exon 8 of 10	ENSP00000395359.2	Q9BY67-1

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 607 AN: 139034 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0246

Gnomad AMR AF: 0.00200

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00574

Gnomad SAS AF: 0.00375

Gnomad FIN AF: 0.000712

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.00105

Gnomad OTH AF: 0.00203

GnomAD2 exomes AF: 0.00270 AC: 574 AN: 212678 AF XY: 0.00252

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.000113

Gnomad EAS exome AF: 0.00618

Gnomad FIN exome AF: 0.000263

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000990

GnomAD4 exome AF: 0.00295 AC: 2315 AN: 785344 Hom.: 2 Cov.: 33 AF XY: 0.00283 AC XY: 1157 AN XY: 409088

African (AFR) AF: 0.0199 AC: 400 AN: 20052

American (AMR) AF: 0.00358 AC: 143 AN: 39926

Ashkenazi Jewish (ASJ) AF: 0.0000558 AC: 1 AN: 17920

East Asian (EAS) AF: 0.0110 AC: 281 AN: 25550

South Asian (SAS) AF: 0.00348 AC: 252 AN: 72310

European-Finnish (FIN) AF: 0.000322 AC: 13 AN: 40370

Middle Eastern (MID) AF: 0.00535 AC: 21 AN: 3922

European-Non Finnish (NFE) AF: 0.00198 AC: 1050 AN: 531266

Other (OTH) AF: 0.00453 AC: 154 AN: 34028

GnomAD4 genome AF: 0.00438 AC: 610 AN: 139158 Hom.: 3 Cov.: 32 AF XY: 0.00421 AC XY: 284 AN XY: 67386

African (AFR) AF: 0.0115 AC: 445 AN: 38730

American (AMR) AF: 0.00200 AC: 28 AN: 14006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3274

East Asian (EAS) AF: 0.00574 AC: 23 AN: 4004

South Asian (SAS) AF: 0.00374 AC: 14 AN: 3746

European-Finnish (FIN) AF: 0.000712 AC: 6 AN: 8422

Middle Eastern (MID) AF: 0.00709 AC: 2 AN: 282

European-Non Finnish (NFE) AF: 0.00105 AC: 67 AN: 63852

Other (OTH) AF: 0.00201 AC: 4 AN: 1988

Alfa AF: 0.000255 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=75/25	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747352768; hg19: chr11-115080311; COSMIC: COSV59023780; COSMIC: COSV59023780;