NM_001301043.2:c.1007C>T

Variant names:

• chr11-115209645-G-A
• rs141892754
• NM_001301043.2:c.1007C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001301043.2(CADM1):​c.1007C>T​(p.Thr336Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,612,888 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (5 hom.)
• Consequence: CADM1 NM_001301043.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.37
• Publications: 6 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007242739).
• BP6: Variant 11-115209645-G-A is Benign according to our data. Variant chr11-115209645-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 782217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 339 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.1007C>T	p.Thr336Ile	missense	Exon 8 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.1007C>T	p.Thr336Ile	missense	Exon 8 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_014333.4		c.1007C>T	p.Thr336Ile	missense	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.1007C>T	p.Thr336Ile	missense	Exon 8 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.1007C>T	p.Thr336Ile	missense	Exon 8 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000452722.7	TSL:1	c.1007C>T	p.Thr336Ile	missense	Exon 8 of 10	ENSP00000395359.2	Q9BY67-1

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 339 AN: 151846 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000871

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00226 AC: 556 AN: 246048 AF XY: 0.00225

Gnomad AFR exome AF: 0.000685

Gnomad AMR exome AF: 0.00383

Gnomad ASJ exome AF: 0.00492

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000955

Gnomad NFE exome AF: 0.00284

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00290 AC: 4242 AN: 1460924 Hom.: 5 Cov.: 36 AF XY: 0.00283 AC XY: 2058 AN XY: 726640

African (AFR) AF: 0.000627 AC: 21 AN: 33476

American (AMR) AF: 0.00429 AC: 192 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 128 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00108 AC: 93 AN: 86166

European-Finnish (FIN) AF: 0.000113 AC: 6 AN: 52890

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5758

European-Non Finnish (NFE) AF: 0.00327 AC: 3630 AN: 1111790

Other (OTH) AF: 0.00270 AC: 163 AN: 60376

GnomAD4 genome AF: 0.00223 AC: 339 AN: 151964 Hom.: 1 Cov.: 32 AF XY: 0.00199 AC XY: 148 AN XY: 74306

African (AFR) AF: 0.000869 AC: 36 AN: 41434

American (AMR) AF: 0.00426 AC: 65 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

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

European-Non Finnish (NFE) AF: 0.00315 AC: 214 AN: 67936

Other (OTH) AF: 0.00190 AC: 4 AN: 2104

Alfa AF: 0.00270 Hom.: 0

Bravo AF: 0.00277

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00314 AC: 27

ExAC AF: 0.00188 AC: 228

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Benign	0.88
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.18	T
Sift4G	Benign	0.086	T
Polyphen		0.017	B
Vest4		0.73
MVP		0.35
MPC		0.71
ClinPred		0.028	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.50
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141892754; hg19: chr11-115080365; COSMIC: COSV104404243;