rs818725

Variant names:

• chr5-33588198-C-G
• rs818725
• NM_030955.4:c.2865+401G>C

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030955.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS12	NM_030955.4	MANE Select	c.2865+401G>C		intron	N/A	NP_112217.2
	ADAMTS12	NM_001324512.2		c.2610+401G>C		intron	N/A	NP_001311441.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS12	ENST00000504830.6	TSL:1 MANE Select	c.2865+401G>C		intron	N/A	ENSP00000422554.1
	ADAMTS12	ENST00000352040.7	TSL:1	c.2610+401G>C		intron	N/A	ENSP00000344847.3
	ADAMTS12	ENST00000504582.5	TSL:5	n.2545+401G>C		intron	N/A

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

African (AFR) AF: 0.177 AC: 7353 AN: 41490

American (AMR) AF: 0.219 AC: 3349 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3470

East Asian (EAS) AF: 0.149 AC: 772 AN: 5164

South Asian (SAS) AF: 0.200 AC: 963 AN: 4824

European-Finnish (FIN) AF: 0.188 AC: 1983 AN: 10548

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17078 AN: 67988

Other (OTH) AF: 0.228 AC: 483 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.66
DANN	Benign	0.68
PhyloP100		-0.93
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: rs818725; hg19: chr5-33588303;