chr10-126140443-C-G

Variant names:

• chr10-126140443-C-G
• rs1551678
• NM_001288973.2:c.340-4783G>C

Variant summary

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

The NM_001288973.2(ADAM12):​c.340-4783G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,020 control chromosomes in the GnomAD database, including 22,742 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 0.54 (22742 hom., cov: 32)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM12	NM_001288973.2	c.340-4783G>C		intron_variant	Intron 4 of 22	ENST00000448723.2	NP_001275902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM12	ENST00000448723.2	c.340-4783G>C		intron_variant	Intron 4 of 22	5	NM_001288973.2	ENSP00000391268.2
ADAM12	ENST00000368679.8	c.349-4783G>C		intron_variant	Intron 4 of 22	1		ENSP00000357668.4
ADAM12	ENST00000368676.8	c.349-4783G>C		intron_variant	Intron 4 of 18	1		ENSP00000357665.4
ADAM12	ENST00000494661.1	n.80-4783G>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81697 AN: 151902 Hom.: 22725 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.538 AC: 81759 AN: 152020 Hom.: 22742 Cov.: 32 AF XY: 0.531 AC XY: 39437 AN XY: 74300

African (AFR) AF: 0.408 AC: 16897 AN: 41440

American (AMR) AF: 0.544 AC: 8312 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2078 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1821 AN: 5164

South Asian (SAS) AF: 0.520 AC: 2503 AN: 4812

European-Finnish (FIN) AF: 0.539 AC: 5695 AN: 10572

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42650 AN: 67966

Other (OTH) AF: 0.545 AC: 1150 AN: 2112

Alfa AF: 0.582 Hom.: 3272

Bravo AF: 0.531

Asia WGS AF: 0.465 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.6
DANN	Benign	0.31
PhyloP100		1.2
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: rs1551678; hg19: chr10-127829012;