rs7076519

Variant names:

• chr10-126060270-T-C
• rs7076519
• NM_001288973.2:c.1609+4536A>G

Variant summary

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

The NM_001288973.2(ADAM12):​c.1609+4536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,076 control chromosomes in the GnomAD database, including 10,463 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 0.36 (10463 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	NM_001288973.2	MANE Select	c.1609+4536A>G		intron	N/A	NP_001275902.1
	ADAM12	NM_003474.6		c.1618+4536A>G		intron	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.1618+4536A>G		intron	N/A	NP_067673.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	ENST00000448723.2	TSL:5 MANE Select	c.1609+4536A>G		intron	N/A	ENSP00000391268.2
	ADAM12	ENST00000368679.8	TSL:1	c.1618+4536A>G		intron	N/A	ENSP00000357668.4
	ADAM12	ENST00000368676.8	TSL:1	c.1618+4536A>G		intron	N/A	ENSP00000357665.4

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54901 AN: 151958 Hom.: 10458 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.361 AC: 54933 AN: 152076 Hom.: 10463 Cov.: 33 AF XY: 0.369 AC XY: 27410 AN XY: 74314

African (AFR) AF: 0.338 AC: 14038 AN: 41474

American (AMR) AF: 0.335 AC: 5124 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3433 AN: 5160

South Asian (SAS) AF: 0.375 AC: 1805 AN: 4816

European-Finnish (FIN) AF: 0.533 AC: 5627 AN: 10566

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23040 AN: 67992

Other (OTH) AF: 0.330 AC: 696 AN: 2106

Alfa AF: 0.332 Hom.: 11262

Bravo AF: 0.347

Asia WGS AF: 0.531 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs7076519; hg19: chr10-127748839;