rs256792

Variant names:

• chr5-33531540-C-T
• rs256792
• NM_030955.4:c.4606+3293G>A

Variant summary

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

The NM_030955.4(ADAMTS12):​c.4606+3293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,062 control chromosomes in the GnomAD database, including 10,766 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 0.36 (10766 hom., cov: 32)
• Consequence: ADAMTS12 NM_030955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS12	NM_030955.4	c.4606+3293G>A		intron_variant	Intron 23 of 23	ENST00000504830.6	NP_112217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS12	ENST00000504830.6	c.4606+3293G>A		intron_variant	Intron 23 of 23	1	NM_030955.4	ENSP00000422554.1
ADAMTS12	ENST00000352040.7	c.4351+3293G>A		intron_variant	Intron 21 of 21	1		ENSP00000344847.3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54251 AN: 151944 Hom.: 10744 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.357 AC: 54316 AN: 152062 Hom.: 10766 Cov.: 32 AF XY: 0.368 AC XY: 27384 AN XY: 74356

African (AFR) AF: 0.419 AC: 17371 AN: 41450

American (AMR) AF: 0.425 AC: 6492 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3470

East Asian (EAS) AF: 0.748 AC: 3864 AN: 5164

South Asian (SAS) AF: 0.562 AC: 2708 AN: 4820

European-Finnish (FIN) AF: 0.307 AC: 3239 AN: 10566

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18798 AN: 67990

Other (OTH) AF: 0.356 AC: 752 AN: 2114

Alfa AF: 0.303 Hom.: 7751

Bravo AF: 0.371

Asia WGS AF: 0.604 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.048
DANN	Benign	0.19
PhyloP100		-1.9
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: rs256792; hg19: chr5-33531645;