rs2548035

chr5-33818046-C-T

Variant summary

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

The NM_030955.4(ADAMTS12):c.489+63073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,842 control chromosomes in the GnomAD database, including 19,082 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 0.49 (19082 hom., cov: 32)
• Consequence: ADAMTS12 NM_030955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

Genes affected

ADAMTS12 (HGNC:14605): (ADAM metallopeptidase with thrombospondin type 1 motif 12) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS-1) motif. Individual members of this family differ in the number of C-terminal TS-1 motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains eight TS-1 motifs. It may play roles in pulmonary cells during fetal development or in tumor processes through its proteolytic activity or as a molecule potentially involved in regulation of cell adhesion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS12	NM_030955.4	c.489+63073G>A		intron_variant		ENST00000504830.6
ADAMTS12	NM_001324511.2	c.489+63073G>A		intron_variant
ADAMTS12	NM_001324512.2	c.489+63073G>A		intron_variant
ADAMTS12	XM_017009905.2	c.489+63073G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS12	ENST00000504830.6	c.489+63073G>A		intron_variant		1	NM_030955.4	P1
ADAMTS12	ENST00000352040.7	c.489+63073G>A		intron_variant		1
ADAMTS12	ENST00000515401.1	c.489+63073G>A		intron_variant		1
ADAMTS12	ENST00000504582.5	n.169+22098G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74658 AN: 151724 Hom.: 19055 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.492 AC: 74724 AN: 151842 Hom.: 19082 Cov.: 32 AF XY: 0.484 AC XY: 35934 AN XY: 74190

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.470

Alfa AF: 0.518 Hom.: 2598

Bravo AF: 0.486

Asia WGS AF: 0.257 AC: 893 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.89
Dann	Benign	0.24

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: rs2548035; hg19: chr5-33818151;