chr5-33529158-T-C

Variant names:

• chr5-33529158-T-C
• rs10521004
• NM_030955.4:c.4607-1792A>G

Variant summary

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

The NM_030955.4(ADAMTS12):​c.4607-1792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,252 control chromosomes in the GnomAD database, including 2,081 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 0.14 (2081 hom., cov: 33)
• Consequence: ADAMTS12 NM_030955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS12	NM_030955.4	c.4607-1792A>G		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.4607-1792A>G		intron_variant	Intron 23 of 23	1	NM_030955.4	ENSP00000422554.1
ADAMTS12	ENST00000352040.7	c.4352-1792A>G		intron_variant	Intron 21 of 21	1		ENSP00000344847.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22016 AN: 152134 Hom.: 2070 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.145 AC: 22052 AN: 152252 Hom.: 2081 Cov.: 33 AF XY: 0.141 AC XY: 10489 AN XY: 74470

African (AFR) AF: 0.260 AC: 10808 AN: 41512

American (AMR) AF: 0.0763 AC: 1167 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3470

East Asian (EAS) AF: 0.0264 AC: 137 AN: 5194

South Asian (SAS) AF: 0.0883 AC: 425 AN: 4812

European-Finnish (FIN) AF: 0.0876 AC: 931 AN: 10624

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7768 AN: 68016

Other (OTH) AF: 0.127 AC: 269 AN: 2116

Alfa AF: 0.120 Hom.: 1777

Bravo AF: 0.149

Asia WGS AF: 0.0920 AC: 319 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	4.7
DANN	Benign	0.56
PhyloP100		0.039
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: rs10521004; hg19: chr5-33529263;