rs2307121

Positions:

• chr5-65329685-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_197941.4(ADAMTS6):​c.1118-202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,018 control chromosomes in the GnomAD database, including 6,524 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 0.27 (6524 hom., cov: 32)
• Consequence: ADAMTS6 NM_197941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

Genes affected

ADAMTS6 (HGNC:222): (ADAM metallopeptidase with thrombospondin type 1 motif 6) 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. Expression of this gene may be regulated by the cytokine TNF-alpha. [provided by RefSeq, Mar 2016]

ADAMTS6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS6	NM_197941.4	c.1118-202G>A		intron_variant		ENST00000381055.8	NP_922932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS6	ENST00000381055.8	c.1118-202G>A		intron_variant		1	NM_197941.4	ENSP00000370443.3
ADAMTS6	ENST00000470597.5	n.1139-202G>A		intron_variant		1
ADAMTS6	ENST00000381052.8	n.*244-202G>A		intron_variant		2		ENSP00000424377.1
ADAMTS6	ENST00000464680.6	n.1136-202G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41399 AN: 151900 Hom.: 6527 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.272 AC: 41397 AN: 152018 Hom.: 6524 Cov.: 32 AF XY: 0.274 AC XY: 20327 AN XY: 74294

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.260

Alfa AF: 0.321 Hom.: 16671

Bravo AF: 0.255

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.82

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: rs2307121; hg19: chr5-64625512;