NM_001301043.2:c.921T>C

Variant names:

• chr11-115214681-A-G
• rs139604912
• NM_001301043.2:c.921T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001301043.2(CADM1):​c.921T>C​(p.Asp307Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,614,050 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (13 hom.)
• Consequence: CADM1 NM_001301043.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.27
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 11-115214681-A-G is Benign according to our data. Variant chr11-115214681-A-G is described in ClinVar as Benign. ClinVar VariationId is 719362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.27 with no splicing effect.
• BS2: High AC in GnomAd4 at 334 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.921T>C	p.Asp307Asp	synonymous	Exon 7 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.921T>C	p.Asp307Asp	synonymous	Exon 7 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_001301045.2		c.921T>C	p.Asp307Asp	synonymous	Exon 7 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.921T>C	p.Asp307Asp	synonymous	Exon 7 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.921T>C	p.Asp307Asp	synonymous	Exon 7 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000536727.5	TSL:1	c.921T>C	p.Asp307Asp	synonymous	Exon 7 of 11	ENSP00000440322.1	X5DQS5

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 334 AN: 152156 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00220 AC: 551 AN: 250994 AF XY: 0.00239

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00281

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00240 AC: 3514 AN: 1461776 Hom.: 13 Cov.: 31 AF XY: 0.00240 AC XY: 1742 AN XY: 727194

African (AFR) AF: 0.000120 AC: 4 AN: 33472

American (AMR) AF: 0.00141 AC: 63 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0129 AC: 338 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.000962 AC: 83 AN: 86258

European-Finnish (FIN) AF: 0.00139 AC: 74 AN: 53412

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5766

European-Non Finnish (NFE) AF: 0.00246 AC: 2735 AN: 1111926

Other (OTH) AF: 0.00316 AC: 191 AN: 60392

GnomAD4 genome AF: 0.00219 AC: 334 AN: 152274 Hom.: 1 Cov.: 32 AF XY: 0.00212 AC XY: 158 AN XY: 74452

African (AFR) AF: 0.000457 AC: 19 AN: 41556

American (AMR) AF: 0.00137 AC: 21 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00316 AC: 215 AN: 68012

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

Alfa AF: 0.00300 Hom.: 1

Bravo AF: 0.00210

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00327

EpiControl AF: 0.00522

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
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.6
DANN	Benign	0.50
PhyloP100		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	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: rs139604912; hg19: chr11-115085401; COSMIC: COSV59024447; COSMIC: COSV59024447;