Variant rs11244787 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.20

Variant links:

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]

ADAM12 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
ADAM12	NM_001288973.2 linkuse as main transcript	c.1918-15T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2 linkuse as main transcript	c.1918-15T>C	splice_polypyrimidine_tract_variant, intron_variant	5	NM_001288973.2	ENSP00000391268	A2
ADAM12	ENST00000368676.8 linkuse as main transcript	c.1927-15T>C	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000357665	A2	O43184-2
ADAM12	ENST00000368679.8 linkuse as main transcript	c.1927-15T>C	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000357668	P2	O43184-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20087

AN:

152068

Hom.:

1417

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.134

AC XY:

96740

AN XY:

724552

show subpopulations

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.:

AF XY:

0.130

AC XY:

9670

AN XY:

74420

show subpopulations

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over