rs6597731

Positions:

• chr10-126021366-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288973.2(ADAM12):​c.2530-1541G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,106 control chromosomes in the GnomAD database, including 31,043 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 0.63 (31043 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.2530-1541G>T		intron_variant		ENST00000448723.2	NP_001275902.1
ADAM12	NM_003474.6	c.2539-1541G>T		intron_variant			NP_003465.3
ADAM12	XM_017016706.2	c.1372-1541G>T		intron_variant			XP_016872195.1
ADAM12	XM_024448210.1	c.1201-1541G>T		intron_variant			XP_024303978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.2530-1541G>T		intron_variant		5	NM_001288973.2	ENSP00000391268	A2
ADAM12	ENST00000368679.8	c.2539-1541G>T		intron_variant		1		ENSP00000357668	P2

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96017 AN: 151990 Hom.: 31017 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.632 AC: 96093 AN: 152106 Hom.: 31043 Cov.: 33 AF XY: 0.631 AC XY: 46905 AN XY: 74362

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.599

Alfa AF: 0.666 Hom.: 4260

Bravo AF: 0.610

Asia WGS AF: 0.723 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs6597731; hg19: chr10-127709935;