NM_001288973.2:c.261-2795G>A

Variant names:

• chr10-126158100-C-T
• rs12778749
• NM_001288973.2:c.261-2795G>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.261-2795G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,038 control chromosomes in the GnomAD database, including 31,947 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 0.64 (31947 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.76
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.261-2795G>A		intron_variant	Intron 3 of 22	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.261-2795G>A		intron_variant	Intron 3 of 22	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.261-2795G>A		intron_variant	Intron 3 of 22	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.261-2795G>A		intron_variant	Intron 3 of 18	1		ENSP00000357665.4

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96781 AN: 151920 Hom.: 31935 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.637 AC: 96832 AN: 152038 Hom.: 31947 Cov.: 33 AF XY: 0.644 AC XY: 47833 AN XY: 74310

African (AFR) AF: 0.451 AC: 18674 AN: 41432

American (AMR) AF: 0.747 AC: 11428 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2543 AN: 3466

East Asian (EAS) AF: 0.768 AC: 3961 AN: 5158

South Asian (SAS) AF: 0.719 AC: 3466 AN: 4818

European-Finnish (FIN) AF: 0.698 AC: 7377 AN: 10568

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46986 AN: 67986

Other (OTH) AF: 0.671 AC: 1417 AN: 2112

Alfa AF: 0.678 Hom.: 114305

Bravo AF: 0.634

Asia WGS AF: 0.718 AC: 2497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.081
DANN	Benign	0.84
PhyloP100		-7.8
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: rs12778749; hg19: chr10-127846669;