rs11244787

Variant names:

• chr10-126046147-A-G
• rs11244787
• NM_001288973.2:c.1918-15T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288973.2(ADAM12):​c.1918-15T>C variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.1918-15T>C		intron_variant	Intron 16 of 22	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.1918-15T>C		intron_variant	Intron 16 of 22	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.1927-15T>C		intron_variant	Intron 16 of 22	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.1927-15T>C		intron_variant	Intron 16 of 18	1		ENSP00000357665.4

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

GnomAD2 exomes AF: 0.134 AC: 33688 AN: 251408 AF XY: 0.137

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 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

African (AFR) AF: 0.131 AC: 4377 AN: 33330

American (AMR) AF: 0.155 AC: 6946 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4802 AN: 26106

East Asian (EAS) AF: 0.0190 AC: 752 AN: 39662

South Asian (SAS) AF: 0.175 AC: 15049 AN: 86126

European-Finnish (FIN) AF: 0.0815 AC: 4351 AN: 53396

Middle Eastern (MID) AF: 0.214 AC: 1229 AN: 5756

European-Non Finnish (NFE) AF: 0.131 AC: 145007 AN: 1106126

Other (OTH) AF: 0.138 AC: 8334 AN: 60208

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

African (AFR) AF: 0.131 AC: 5448 AN: 41488

American (AMR) AF: 0.153 AC: 2347 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3470

East Asian (EAS) AF: 0.0261 AC: 135 AN: 5178

South Asian (SAS) AF: 0.167 AC: 806 AN: 4824

European-Finnish (FIN) AF: 0.0869 AC: 923 AN: 10620

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9194 AN: 67994

Other (OTH) AF: 0.152 AC: 321 AN: 2116

Alfa AF: 0.141 Hom.: 335

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
PhyloP100		4.2
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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