10-126158045-G-T

Variant names:

• chr10-126158045-G-T
• rs10901542
• NM_001288973.2:c.261-2740C>A

Variant summary

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

The NM_001288973.2(ADAM12):​c.261-2740C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,088 control chromosomes in the GnomAD database, including 31,609 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 (31609 hom., cov: 33)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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=-0.84).
• 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.261-2740C>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.261-2740C>A		intron_variant	Intron 3 of 22	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.261-2740C>A		intron_variant	Intron 3 of 22	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.261-2740C>A		intron_variant	Intron 3 of 18	1		ENSP00000357665.4

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95980 AN: 151970 Hom.: 31596 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.631 AC: 96031 AN: 152088 Hom.: 31609 Cov.: 33 AF XY: 0.638 AC XY: 47445 AN XY: 74336

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.667

Alfa AF: 0.656 Hom.: 4169

Bravo AF: 0.628

Asia WGS AF: 0.716 AC: 2488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.76

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: rs10901542; hg19: chr10-127846614;