rs1476083

Positions:

• chr5-129602436-A-T

Variant summary

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

The NM_133638.6(ADAMTS19):​c.1478+5772A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,026 control chromosomes in the GnomAD database, including 26,936 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 0.58 (26936 hom., cov: 32)
• Consequence: ADAMTS19 NM_133638.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918

Genes affected

ADAMTS19 (HGNC:17111): (ADAM metallopeptidase with thrombospondin type 1 motif 19) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) 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 protein encoded by this gene has high sequence similarity to the protein encoded by ADAMTS16, another family member. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS19	NM_133638.6	c.1478+5772A>T		intron_variant		ENST00000274487.9	NP_598377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS19	ENST00000274487.9	c.1478+5772A>T		intron_variant		1	NM_133638.6	ENSP00000274487	P1
	ENST00000503616.5	n.405-101849T>A		intron_variant, non_coding_transcript_variant		3
	ENST00000653455.1	n.377-3350T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87835 AN: 151908 Hom.: 26944 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.578 AC: 87849 AN: 152026 Hom.: 26936 Cov.: 32 AF XY: 0.578 AC XY: 42948 AN XY: 74308

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.603

Alfa AF: 0.618 Hom.: 3740

Bravo AF: 0.564

Asia WGS AF: 0.530 AC: 1847 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	3.3
DANN	Benign	0.56

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: rs1476083; hg19: chr5-128938129;