11-115209591-ATGGTGGTGG-A

Variant names:

• chr11-115209591-ATGGTGGTGG-A
• rs747352768
• NM_001301043.2:c.1052_1060delCCACCACCA

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_001301043.2(CADM1):​c.1052_1060delCCACCACCA​(p.Thr351_Thr353del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000772 in 924,982 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (1 hom.)
• Consequence: CADM1 NM_001301043.2 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.96
• 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 -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001301043.2
• BP6: Variant 11-115209591-ATGGTGGTGG-A is Benign according to our data. Variant chr11-115209591-ATGGTGGTGG-A is described in ClinVar as Benign. ClinVar VariationId is 733505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 78 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.1052_1060delCCACCACCA	p.Thr351_Thr353del	disruptive_inframe_deletion	Exon 8 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.1052_1060delCCACCACCA	p.Thr351_Thr353del	disruptive_inframe_deletion	Exon 8 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_014333.4		c.1052_1060delCCACCACCA	p.Thr351_Thr353del	disruptive_inframe_deletion	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.1052_1060delCCACCACCA	p.Thr351_Thr353del	disruptive_inframe_deletion	Exon 8 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.1052_1060delCCACCACCA	p.Thr351_Thr353del	disruptive_inframe_deletion	Exon 8 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000452722.7	TSL:1	c.1052_1060delCCACCACCA	p.Thr351_Thr353del	disruptive_inframe_deletion	Exon 8 of 10	ENSP00000395359.2	Q9BY67-1

Frequencies

GnomAD3 genomes AF: 0.000547 AC: 76 AN: 139038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000715

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.00107

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000626

Gnomad OTH AF: 0.000509

GnomAD2 exomes AF: 0.00122 AC: 259 AN: 212678 AF XY: 0.00123

Gnomad AFR exome AF: 0.000219

Gnomad AMR exome AF: 0.0000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0141

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000165

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.000809 AC: 636 AN: 785820 Hom.: 1 AF XY: 0.000845 AC XY: 346 AN XY: 409302

African (AFR) AF: 0.000349 AC: 7 AN: 20070

American (AMR) AF: 0.000100 AC: 4 AN: 39932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17920

East Asian (EAS) AF: 0.0136 AC: 347 AN: 25550

South Asian (SAS) AF: 0.00134 AC: 97 AN: 72316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40370

Middle Eastern (MID) AF: 0.000255 AC: 1 AN: 3922

European-Non Finnish (NFE) AF: 0.000269 AC: 143 AN: 531702

Other (OTH) AF: 0.00109 AC: 37 AN: 34038

GnomAD4 genome AF: 0.000560 AC: 78 AN: 139162 Hom.: 0 Cov.: 32 AF XY: 0.000742 AC XY: 50 AN XY: 67384

African (AFR) AF: 0.000310 AC: 12 AN: 38730

American (AMR) AF: 0.0000714 AC: 1 AN: 14006

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

East Asian (EAS) AF: 0.0135 AC: 54 AN: 4006

South Asian (SAS) AF: 0.00107 AC: 4 AN: 3744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000626 AC: 4 AN: 63854

Other (OTH) AF: 0.00151 AC: 3 AN: 1988

Alfa AF: 0.0000730 Hom.: 0

Bravo AF: 0.000695

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0
Mutation Taster		=93/107	disease causing

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;