10-126079541-C-T

Variant names:

• chr10-126079541-C-T
• rs1380439
• NM_001288973.2:c.1146-7887G>A

Variant summary

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

The NM_001288973.2(ADAM12):​c.1146-7887G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,050 control chromosomes in the GnomAD database, including 7,130 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 0.30 (7130 hom., cov: 32)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	NM_001288973.2	MANE Select	c.1146-7887G>A		intron	N/A	NP_001275902.1	Q5JRP2
	ADAM12	NM_003474.6		c.1155-7887G>A		intron	N/A	NP_003465.3
	ADAM12	NM_021641.5		c.1155-7887G>A		intron	N/A	NP_067673.2	O43184-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM12	ENST00000448723.2	TSL:5 MANE Select	c.1146-7887G>A		intron	N/A	ENSP00000391268.2	Q5JRP2
	ADAM12	ENST00000368679.8	TSL:1	c.1155-7887G>A		intron	N/A	ENSP00000357668.4	O43184-1
	ADAM12	ENST00000368676.8	TSL:1	c.1155-7887G>A		intron	N/A	ENSP00000357665.4	O43184-2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45944 AN: 151932 Hom.: 7123 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.303 AC: 46003 AN: 152050 Hom.: 7130 Cov.: 32 AF XY: 0.303 AC XY: 22531 AN XY: 74318

African (AFR) AF: 0.306 AC: 12692 AN: 41474

American (AMR) AF: 0.232 AC: 3536 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 866 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2008 AN: 5170

South Asian (SAS) AF: 0.422 AC: 2037 AN: 4824

European-Finnish (FIN) AF: 0.353 AC: 3725 AN: 10556

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20266 AN: 67970

Other (OTH) AF: 0.258 AC: 543 AN: 2108

Alfa AF: 0.285 Hom.: 19969

Bravo AF: 0.287

Asia WGS AF: 0.379 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.32
PhyloP100		-0.51
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: rs1380439; hg19: chr10-127768110;