rs59795197

Variant names:

• chr5-157416149-C-T
• rs59795197
• ENST00000519499.2:c.-2232-39643G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000519499.2(ENSG00000285868):​c.-2232-39643G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 152,030 control chromosomes in the GnomAD database, including 739 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 0.088 (739 hom., cov: 32)
• Consequence: ENSG00000285868 ENST00000519499.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 1 publications found

Genes affected

ENSG00000285868 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPAL4-DT	NR_136204.1	n.94-39643G>A		intron_variant	Intron 1 of 3
NIPAL4-DT	NR_136205.1	n.93+43859G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285868	ENST00000519499.2	c.-2232-39643G>A		intron_variant	Intron 1 of 5	3		ENSP00000496943.1
ADAM19	ENST00000517951.5	n.*1742-17935G>A		intron_variant	Intron 21 of 22	2		ENSP00000428376.1

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13405 AN: 151912 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0881 AC: 13397 AN: 152030 Hom.: 739 Cov.: 32 AF XY: 0.0923 AC XY: 6859 AN XY: 74288

African (AFR) AF: 0.0230 AC: 955 AN: 41490

American (AMR) AF: 0.0778 AC: 1189 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3468

East Asian (EAS) AF: 0.186 AC: 963 AN: 5174

South Asian (SAS) AF: 0.139 AC: 671 AN: 4816

European-Finnish (FIN) AF: 0.162 AC: 1711 AN: 10552

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7161 AN: 67930

Other (OTH) AF: 0.0795 AC: 168 AN: 2114

Alfa AF: 0.0907 Hom.: 86

Bravo AF: 0.0789

Asia WGS AF: 0.125 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.40
PhyloP100		0.076
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs59795197; hg19: chr5-156843157;