rs11244787

chr10-126046147-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288973.2(ADAM12):c.1918-15T>C variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.131 in 1,607,608 control chromosomes in the GnomAD database, including 14,580 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1423 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13157 hom.)
• Consequence: ADAM12 NM_001288973.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20

Genes affected

ADAM12 (HGNC:190): (ADAM metallopeptidase domain 12) This gene encodes a member of a family of proteins that are structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM12	NM_001288973.2	c.1918-15T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000448723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM12	ENST00000448723.2	c.1918-15T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001288973.2	A2
ADAM12	ENST00000368676.8	c.1927-15T>C		splice_polypyrimidine_tract_variant, intron_variant		1		A2
ADAM12	ENST00000368679.8	c.1927-15T>C		splice_polypyrimidine_tract_variant, intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20087 AN: 152068 Hom.: 1417 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.134 AC: 33688 AN: 251408 Hom.: 2539 AF XY: 0.137 AC XY: 18671 AN XY: 135876

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.0290

Gnomad SAS exome AF: 0.177

Gnomad FIN exome AF: 0.0812

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.131 AC: 190847 AN: 1455422 Hom.: 13157 Cov.: 30 AF XY: 0.134 AC XY: 96740 AN XY: 724552

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.0190

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.0815

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.132 AC: 20109 AN: 152186 Hom.: 1423 Cov.: 32 AF XY: 0.130 AC XY: 9670 AN XY: 74420

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0261

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0869

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.152

Alfa AF: 0.141 Hom.: 327

Bravo AF: 0.136

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	11
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11244787; hg19: chr10-127734716; COSMIC: COSV64116756; COSMIC: COSV64116756;