rs1476083

Variant names:

• chr5-129602436-A-T
• rs1476083
• NM_133638.6:c.1478+5772A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ADAMTS19 Gene-Disease associations (from GenCC):

• cardiac valvular dysplasia 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• congenital heart disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

CHSY3-AS1 (HGNC:58253):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133638.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS19	NM_133638.6	MANE Select	c.1478+5772A>T		intron	N/A	NP_598377.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS19	ENST00000274487.9	TSL:1 MANE Select	c.1478+5772A>T		intron	N/A	ENSP00000274487.5
	ADAMTS19	ENST00000913209.1		c.1601+5772A>T		intron	N/A	ENSP00000583268.1
	ADAMTS19	ENST00000913210.1		c.1478+5772A>T		intron	N/A	ENSP00000583269.1

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

African (AFR) AF: 0.360 AC: 14899 AN: 41436

American (AMR) AF: 0.604 AC: 9223 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2237 AN: 3468

East Asian (EAS) AF: 0.575 AC: 2970 AN: 5162

South Asian (SAS) AF: 0.606 AC: 2921 AN: 4820

European-Finnish (FIN) AF: 0.667 AC: 7038 AN: 10558

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46605 AN: 67988

Other (OTH) AF: 0.603 AC: 1275 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		0.92
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: rs1476083; hg19: chr5-128938129;