rs747352768

Variant names:

• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-A
• rs747352768
• NM_001301043.2:c.1040_1060delCCACCACCACCACCACCACCA

Your query was ambiguous. Multiple possible variants found:

• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-A
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGGTGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGG
• chr11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGGTGG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001301043.2(CADM1):​c.1040_1060delCCACCACCACCACCACCACCA​(p.Thr347_Thr353del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000227 in 924,884 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: CADM1 NM_001301043.2 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001301043.2

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.1040_1060delCCACCACCACCACCACCACCA	p.Thr347_Thr353del	disruptive_inframe_deletion	Exon 8 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.1040_1060delCCACCACCACCACCACCACCA	p.Thr347_Thr353del	disruptive_inframe_deletion	Exon 8 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_014333.4		c.1040_1060delCCACCACCACCACCACCACCA	p.Thr347_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.1040_1060delCCACCACCACCACCACCACCA	p.Thr347_Thr353del	disruptive_inframe_deletion	Exon 8 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.1040_1060delCCACCACCACCACCACCACCA	p.Thr347_Thr353del	disruptive_inframe_deletion	Exon 8 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000452722.7	TSL:1	c.1040_1060delCCACCACCACCACCACCACCA	p.Thr347_Thr353del	disruptive_inframe_deletion	Exon 8 of 10	ENSP00000395359.2	Q9BY67-1

Frequencies

GnomAD3 genomes AF: 0.0000288 AC: 4 AN: 139040 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000286

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

GnomAD4 exome AF: 0.0000216 AC: 17 AN: 785844 Hom.: 0 AF XY: 0.0000195 AC XY: 8 AN XY: 409310

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20070

American (AMR) AF: 0.0000501 AC: 2 AN: 39932

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 25552

South Asian (SAS) AF: 0.00 AC: 0 AN: 72320

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3922

European-Non Finnish (NFE) AF: 0.0000282 AC: 15 AN: 531720

Other (OTH) AF: 0.00 AC: 0 AN: 34038

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000746656), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000288 AC: 4 AN: 139040 Hom.: 0 Cov.: 32 AF XY: 0.0000297 AC XY: 2 AN XY: 67278

African (AFR) AF: 0.00 AC: 0 AN: 38640

American (AMR) AF: 0.000286 AC: 4 AN: 13982

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4006

South Asian (SAS) AF: 0.00 AC: 0 AN: 3734

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63854

Other (OTH) AF: 0.00 AC: 0 AN: 1966

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0
Mutation Taster		=89/111	disease causing (long InDel)

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;