rs1459709

Variant names:

• chr10-126184259-G-A
• rs1459709
• NM_001288973.2:c.261-28954C>T

Variant summary

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

The NM_001288973.2(ADAM12):​c.261-28954C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,156 control chromosomes in the GnomAD database, including 3,429 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 0.19 (3429 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 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.261-28954C>T		intron	N/A	NP_001275902.1
	ADAM12	NM_003474.6		c.261-28954C>T		intron	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.261-28954C>T		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.261-28954C>T		intron	N/A	ENSP00000391268.2
	ADAM12	ENST00000368679.8	TSL:1	c.261-28954C>T		intron	N/A	ENSP00000357668.4
	ADAM12	ENST00000368676.8	TSL:1	c.261-28954C>T		intron	N/A	ENSP00000357665.4

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29635 AN: 152036 Hom.: 3426 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.195 AC: 29634 AN: 152156 Hom.: 3429 Cov.: 33 AF XY: 0.188 AC XY: 14019 AN XY: 74378

African (AFR) AF: 0.109 AC: 4510 AN: 41498

American (AMR) AF: 0.194 AC: 2974 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1247 AN: 3472

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5180

South Asian (SAS) AF: 0.158 AC: 761 AN: 4828

European-Finnish (FIN) AF: 0.166 AC: 1756 AN: 10570

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17529 AN: 67994

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.236 Hom.: 2470

Bravo AF: 0.193

Asia WGS AF: 0.117 AC: 409 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.025
DANN	Benign	0.64
PhyloP100		-1.5
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: rs1459709; hg19: chr10-127872828;