rs818725

Positions:

• chr5-33588198-C-G

Variant summary

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

The NM_030955.4(ADAMTS12):​c.2865+401G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,076 control chromosomes in the GnomAD database, including 3,732 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 0.22 (3732 hom., cov: 32)
• Consequence: ADAMTS12 NM_030955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS12	NM_030955.4	c.2865+401G>C		intron_variant		ENST00000504830.6	NP_112217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS12	ENST00000504830.6	c.2865+401G>C		intron_variant		1	NM_030955.4	ENSP00000422554	P1
ADAMTS12	ENST00000352040.7	c.2610+401G>C		intron_variant		1		ENSP00000344847
ADAMTS12	ENST00000504582.5	n.2545+401G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33118 AN: 151958 Hom.: 3726 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.218 AC: 33146 AN: 152076 Hom.: 3732 Cov.: 32 AF XY: 0.216 AC XY: 16074 AN XY: 74304

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.228

Alfa AF: 0.237 Hom.: 536

Bravo AF: 0.218

Asia WGS AF: 0.200 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.66
DANN	Benign	0.68

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: rs818725; hg19: chr5-33588303;