5-157460125-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000517951.5(ADAM19):n.*1741+28140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,410,364 control chromosomes in the GnomAD database, including 90,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11148 hom., cov: 33)

Exomes 𝑓: 0.35 ( 79010 hom. )

Consequence

ADAM19
ENST00000517951.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.658

Variant links:

Genes affected

ADAM19 (HGNC:197): (ADAM metallopeptidase domain 19) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has been demonstrated to be an active metalloproteinase, which may be involved in normal physiological processes such as cell migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. It is proposed to play a role in pathological processes, such as cancer, inflammatory diseases, renal diseases, and Alzheimer's disease. [provided by RefSeq, May 2013]

ADAM19 links:

ENSG00000285868 (HGNC:):

ENSG00000285868 links:

NIPAL4-DT (HGNC:55542): (NIPAL4 divergent transcript)

NIPAL4-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 5-157460125-A-G is Benign according to our data. Variant chr5-157460125-A-G is described in ClinVar as [Benign]. Clinvar id is 257433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-157460125-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPAL4-DT	NR_136204.1 link	n.-25T>C		upstream_gene_variant
NIPAL4-DT	NR_136205.1 link	n.-25T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000517951.5 link	n.*1741+28140T>C		intron_variant	Intron 21 of 22	2		ENSP00000428376.1		E5RIS2
ENSG00000285868	ENST00000519499.2 link	c.-2350T>C		upstream_gene_variant		3		ENSP00000496943.1

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57139

AN:

151908

Hom.:

11131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.720

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.368

AC:

17039

AN:

46260

Hom.:

3459

AF XY:

0.371

AC XY:

8811

AN XY:

23770

show subpopulations

Gnomad AFR exome

AF:

0.373

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.328

Gnomad EAS exome

AF:

0.711

Gnomad SAS exome

AF:

0.357

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.333

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.348

AC:

438407

AN:

1258338

Hom.:

79010

Cov.:

AF XY:

0.348

AC XY:

212080

AN XY:

609606

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.671

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.338

Gnomad4 OTH exome

AF:

0.361

GnomAD4 genome

AF:

0.376

AC:

57188

AN:

152026

Hom.:

11148

Cov.:

AF XY:

0.379

AC XY:

28202

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.392

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.720

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.350

Gnomad4 OTH

AF:

0.374

Alfa

AF:

0.363

Hom.:

1591

Bravo

AF:

0.373

Asia WGS

AF:

0.537

AC:

1868

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Autosomal recessive congenital ichthyosis 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over