Genetic Variant ADAMTS19-AS1:n.137-44844T>C (chr5-129396979-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000723046.1(ADAMTS19-AS1):n.137-44844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,320 control chromosomes in the GnomAD database, including 9,912 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 0.33 ( 9893 hom., cov: 31)

Exomes 𝑓: 0.31 ( 19 hom. )

Consequence

ADAMTS19-AS1
ENST00000723046.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140

Publications

3 publications found

Variant links:

Genes affected

ADAMTS19-AS1 (HGNC:40797): (ADAMTS19 antisense RNA 1)

ADAMTS19-AS1 links:

MIR4460 (HGNC:41795): (microRNA 4460) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4460 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000723046.1. 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
	MIR4460	NR_039665.1		n.*83T>C		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ADAMTS19-AS1	ENST00000723046.1		n.137-44844T>C	intron	N/A
ADAMTS19-AS1	ENST00000723047.1		n.1062-35405T>C	intron	N/A
MIR4460	ENST00000577862.1	TSL:6	n.*83T>C	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49850

AN:

151858

Hom.:

9888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0985

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.363

GnomAD4 exome

AF:

0.314

AC:

108

AN:

344

Hom.:

AF XY:

0.300

AC XY:

AN XY:

190

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.375

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

0.302

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.417

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.328

AC:

49860

AN:

151976

Hom.:

9893

Cov.:

AF XY:

0.333

AC XY:

24701

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.0984

AC:

4086

AN:

41544

American (AMR)

AF:

0.421

AC:

6437

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1328

AN:

3468

East Asian (EAS)

AF:

0.221

AC:

1123

AN:

5080

South Asian (SAS)

AF:

0.315

AC:

1515

AN:

4812

European-Finnish (FIN)

AF:

0.518

AC:

5468

AN:

10558

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28606

AN:

67932

Other (OTH)

AF:

0.358

AC:

754

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1530

3060

4589

6119

7649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.377

Hom.:

17261

Bravo

AF:

0.313

Asia WGS

AF:

0.242

AC:

845

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

(source)

DANN

Benign

0.32

PhyloP100

0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over