chr11-115229156-C-T

Variant names:

• chr11-115229156-C-T
• rs138595924
• NM_001301043.2:c.678G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001301043.2(CADM1):​c.678G>A​(p.Ala226Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,614,014 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (20 hom., cov: 33)
  • Exomes 𝑓: 0.00075 (15 hom.)
• Consequence: CADM1 NM_001301043.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.37
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.112).
• BP6: Variant 11-115229156-C-T is Benign according to our data. Variant chr11-115229156-C-T is described in ClinVar as Benign. ClinVar VariationId is 779315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.37 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00772 (1176/152302) while in subpopulation AFR AF = 0.0268 (1113/41554). AF 95% confidence interval is 0.0255. There are 20 homozygotes in GnomAd4. There are 536 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1176 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.678G>A	p.Ala226Ala	synonymous	Exon 5 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.678G>A	p.Ala226Ala	synonymous	Exon 5 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_001301045.2		c.678G>A	p.Ala226Ala	synonymous	Exon 5 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.678G>A	p.Ala226Ala	synonymous	Exon 5 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.678G>A	p.Ala226Ala	synonymous	Exon 5 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000536727.5	TSL:1	c.678G>A	p.Ala226Ala	synonymous	Exon 5 of 11	ENSP00000440322.1	X5DQS5

Frequencies

GnomAD3 genomes AF: 0.00773 AC: 1177 AN: 152184 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00206 AC: 517 AN: 250820 AF XY: 0.00145

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000749 AC: 1095 AN: 1461712 Hom.: 15 Cov.: 31 AF XY: 0.000666 AC XY: 484 AN XY: 727162

African (AFR) AF: 0.0265 AC: 887 AN: 33478

American (AMR) AF: 0.00145 AC: 65 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5722

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111962

Other (OTH) AF: 0.00136 AC: 82 AN: 60384

GnomAD4 genome AF: 0.00772 AC: 1176 AN: 152302 Hom.: 20 Cov.: 33 AF XY: 0.00720 AC XY: 536 AN XY: 74472

African (AFR) AF: 0.0268 AC: 1113 AN: 41554

American (AMR) AF: 0.00235 AC: 36 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68026

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00352 Hom.: 4

Bravo AF: 0.00890

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.6
DANN	Benign	0.65
PhyloP100		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs138595924; hg19: chr11-115099876; COSMIC: COSV59004519; COSMIC: COSV59004519;