5-33769948-C-T

Variant names:

• chr5-33769948-C-T
• rs1423485
• NM_030955.4:c.490-18400G>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.490-18400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,174 control chromosomes in the GnomAD database, including 1,567 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 0.13 (1567 hom., cov: 32)
• Consequence: ADAMTS12 NM_030955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS12	NM_030955.4	c.490-18400G>A		intron_variant	Intron 2 of 23	ENST00000504830.6	NP_112217.2
ADAMTS12	NM_001324512.2	c.490-18400G>A		intron_variant	Intron 2 of 21		NP_001311441.1
ADAMTS12	NM_001324511.2	c.490-18400G>A		intron_variant	Intron 2 of 2		NP_001311440.1
ADAMTS12	XM_017009905.2	c.490-18400G>A		intron_variant	Intron 2 of 24		XP_016865394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS12	ENST00000504830.6	c.490-18400G>A		intron_variant	Intron 2 of 23	1	NM_030955.4	ENSP00000422554.1
ADAMTS12	ENST00000352040.7	c.490-18400G>A		intron_variant	Intron 2 of 21	1		ENSP00000344847.3
ADAMTS12	ENST00000515401.1	c.490-18400G>A		intron_variant	Intron 2 of 2	1		ENSP00000421638.1
ADAMTS12	ENST00000504582.5	n.170-18400G>A		intron_variant	Intron 1 of 17	5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19085 AN: 152056 Hom.: 1565 Cov.: 32

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.125 AC: 19086 AN: 152174 Hom.: 1567 Cov.: 32 AF XY: 0.128 AC XY: 9541 AN XY: 74398

African (AFR) AF: 0.0755 AC: 3135 AN: 41522

American (AMR) AF: 0.148 AC: 2253 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 453 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2079 AN: 5156

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4818

European-Finnish (FIN) AF: 0.0801 AC: 849 AN: 10600

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8389 AN: 68016

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.135 Hom.: 1223

Bravo AF: 0.127

Asia WGS AF: 0.283 AC: 984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		0.32
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: rs1423485; hg19: chr5-33770053;