rs145894931

Variant names:

• chr11-115217963-A-C
• rs145894931
• NM_001301043.2:c.750T>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001301043.2(CADM1):​c.750T>G​(p.Thr250Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,613,424 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: CADM1 NM_001301043.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.704
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.059).
• BP6: Variant 11-115217963-A-C is Benign according to our data. Variant chr11-115217963-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2642395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.704 with no splicing effect.
• 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.750T>G	p.Thr250Thr	synonymous	Exon 6 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.750T>G	p.Thr250Thr	synonymous	Exon 6 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_001301045.2		c.750T>G	p.Thr250Thr	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.750T>G	p.Thr250Thr	synonymous	Exon 6 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.750T>G	p.Thr250Thr	synonymous	Exon 6 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000536727.5	TSL:1	c.750T>G	p.Thr250Thr	synonymous	Exon 6 of 11	ENSP00000440322.1	X5DQS5

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00788

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000976 AC: 245 AN: 251104 AF XY: 0.000973

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00527

Gnomad EAS exome AF: 0.00747

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000395 AC: 577 AN: 1461106 Hom.: 2 Cov.: 30 AF XY: 0.000409 AC XY: 297 AN XY: 726902

African (AFR) AF: 0.0000598 AC: 2 AN: 33434

American (AMR) AF: 0.0000447 AC: 2 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 98 AN: 26112

East Asian (EAS) AF: 0.00484 AC: 192 AN: 39666

South Asian (SAS) AF: 0.000719 AC: 62 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.000157 AC: 175 AN: 1111412

Other (OTH) AF: 0.000713 AC: 43 AN: 60346

GnomAD4 genome AF: 0.000512 AC: 78 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000551 AC XY: 41 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.00810 AC: 42 AN: 5188

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68036

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000686 Hom.: 0

Bravo AF: 0.000635

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000415

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
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.5
DANN	Benign	0.76
PhyloP100		0.70
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: rs145894931; hg19: chr11-115088683;