chr11-130405451-G-A

Position:

• chr11-130405451-G-A

Variant summary

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

The NM_007037.6(ADAMTS8):​c.*107C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 1,498,332 control chromosomes in the GnomAD database, including 6,452 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 0.12 (1374 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5078 hom.)
• Consequence: ADAMTS8 NM_007037.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

Genes affected

ADAMTS8 (HGNC:224): (ADAM metallopeptidase with thrombospondin type 1 motif 8) 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) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs, and disrupts angiogenesis in vivo. A number of disorders have been mapped in the vicinity of this gene, most notably lung neoplasms. Reduced expression of this gene has been observed in multiple human cancers and this gene has been proposed as a potential tumor suppressor. [provided by RefSeq, Feb 2016]

ADAMTS8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS8	NM_007037.6	c.*107C>T		3_prime_UTR_variant	9/9	ENST00000257359.7	NP_008968.4
ADAMTS8	XM_017017145.2	c.*107C>T		3_prime_UTR_variant	9/9		XP_016872634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS8	ENST00000257359	c.*107C>T		3_prime_UTR_variant	9/9	1	NM_007037.6	ENSP00000257359.6
ADAMTS8	ENST00000531752.1	n.1724C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17869 AN: 152068 Hom.: 1372 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0968

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0786 AC: 105762 AN: 1346146 Hom.: 5078 Cov.: 30 AF XY: 0.0797 AC XY: 52507 AN XY: 658784

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.0769

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0524

Gnomad4 NFE exome AF: 0.0671

Gnomad4 OTH exome AF: 0.0915

GnomAD4 genome AF: 0.118 AC: 17894 AN: 152186 Hom.: 1374 Cov.: 32 AF XY: 0.116 AC XY: 8613 AN XY: 74394

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0968

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0532

Gnomad4 NFE AF: 0.0695

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0784 Hom.: 1201

Bravo AF: 0.126

Asia WGS AF: 0.144 AC: 501 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	1.2
DANN	Benign	0.52

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: rs2242312; hg19: chr11-130275346;