ENST00000517951.5:n.*1741+28056G>A

Variant names:

• chr5-157460209-C-T
• rs369508909
• ENST00000517951.5:n.*1741+28056G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000517951.5(ADAM19):​n.*1741+28056G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000615 in 1,485,562 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (2 hom.)
• Consequence: ADAM19 ENST00000517951.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0450
• Publications: 0 publications found

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]

NIPAL4 (HGNC:28018): (NIPA like domain containing 4) This gene likely encodes a membrane receptor. Mutations in this gene have been associated with autosomal recessive congenital ichthyosis. [provided by RefSeq, Feb 2010]

ENSG00000285868 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-157460209-C-T is Benign according to our data. Variant chr5-157460209-C-T is described in ClinVar as Benign. ClinVar VariationId is 2763581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517951.5. 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
	NIPAL4	NM_001099287.2	MANE Select	c.-112C>T		upstream_gene	N/A	NP_001092757.2	Q0D2K0-1
	NIPAL4	NM_001172292.2		c.-112C>T		upstream_gene	N/A	NP_001165763.2	Q0D2K0-2
	NIPAL4-DT	NR_136204.1		n.-109G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	ENST00000517951.5	TSL:2	n.*1741+28056G>A		intron	N/A	ENSP00000428376.1	E5RIS2
	NIPAL4	ENST00000311946.8	TSL:1 MANE Select	c.-112C>T		upstream_gene	N/A	ENSP00000311687.8	Q0D2K0-1
	ENSG00000285868	ENST00000519499.2	TSL:3	c.-2434G>A		upstream_gene	N/A	ENSP00000496943.1

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 504 AN: 152192 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000719 AC: 65 AN: 90410 AF XY: 0.000633

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.000560

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000308 AC: 410 AN: 1333254 Hom.: 2 Cov.: 32 AF XY: 0.000288 AC XY: 188 AN XY: 653184

African (AFR) AF: 0.0136 AC: 368 AN: 27062

American (AMR) AF: 0.000454 AC: 12 AN: 26414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20416

East Asian (EAS) AF: 0.0000303 AC: 1 AN: 32964

South Asian (SAS) AF: 0.00 AC: 0 AN: 68086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4896

European-Non Finnish (NFE) AF: 0.00000475 AC: 5 AN: 1052766

Other (OTH) AF: 0.000437 AC: 24 AN: 54882

GnomAD4 genome AF: 0.00331 AC: 504 AN: 152308 Hom.: 5 Cov.: 33 AF XY: 0.00285 AC XY: 212 AN XY: 74484

African (AFR) AF: 0.0117 AC: 488 AN: 41574

American (AMR) AF: 0.000718 AC: 11 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00284 Hom.: 0

Bravo AF: 0.00352

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		0.045
PromoterAI		0.16	Neutral
Mutation Taster		=100/0	polymorphism

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: rs369508909; hg19: chr5-156887217;