rs1423300

Positions:

• chr5-33832328-G-A
• chr5-33832328-G-C

Variant summary

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

The NM_030955.4(ADAMTS12):​c.489+48791C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,012 control chromosomes in the GnomAD database, including 19,243 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 0.46 (19243 hom., cov: 32)
• Consequence: ADAMTS12 NM_030955.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS12	NM_030955.4	c.489+48791C>T		intron_variant		ENST00000504830.6	NP_112217.2
ADAMTS12	NM_001324511.2	c.489+48791C>T		intron_variant			NP_001311440.1
ADAMTS12	NM_001324512.2	c.489+48791C>T		intron_variant			NP_001311441.1
ADAMTS12	XM_017009905.2	c.489+48791C>T		intron_variant			XP_016865394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS12	ENST00000504830.6	c.489+48791C>T		intron_variant		1	NM_030955.4	ENSP00000422554	P1
ADAMTS12	ENST00000352040.7	c.489+48791C>T		intron_variant		1		ENSP00000344847
ADAMTS12	ENST00000515401.1	c.489+48791C>T		intron_variant		1		ENSP00000421638
ADAMTS12	ENST00000504582.5	n.169+7816C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69057 AN: 151892 Hom.: 19187 Cov.: 32

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.455 AC: 69175 AN: 152012 Hom.: 19243 Cov.: 32 AF XY: 0.460 AC XY: 34187 AN XY: 74292

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.445

Alfa AF: 0.324 Hom.: 6557

Bravo AF: 0.484

Asia WGS AF: 0.560 AC: 1946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.012
DANN	Benign	0.46

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: rs1423300; hg19: chr5-33832433;