chr5-157459842-A-G

Variant names:

• chr5-157459842-A-G
• rs77058781
• ENST00000519499.2:c.-2233+166T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000519499.2(ENSG00000285868):​c.-2233+166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 152,220 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.081 (596 hom., cov: 32)
• Consequence: ENSG00000285868 ENST00000519499.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-157459842-A-G is Benign according to our data. Variant chr5-157459842-A-G is described in ClinVar as Benign. ClinVar VariationId is 1228213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000519499.2. 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-DT	NR_136204.1		n.93+166T>C		intron	N/A
	NIPAL4-DT	NR_136205.1		n.93+166T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285868	ENST00000519499.2	TSL:3	c.-2233+166T>C		intron	N/A	ENSP00000496943.1
	ADAM19	ENST00000517951.5	TSL:2	n.*1741+28423T>C		intron	N/A	ENSP00000428376.1	E5RIS2

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12296 AN: 152102 Hom.: 595 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0617

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0941

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0808 AC: 12292 AN: 152220 Hom.: 596 Cov.: 32 AF XY: 0.0842 AC XY: 6265 AN XY: 74418

African (AFR) AF: 0.0270 AC: 1122 AN: 41562

American (AMR) AF: 0.0651 AC: 996 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3468

East Asian (EAS) AF: 0.156 AC: 805 AN: 5164

South Asian (SAS) AF: 0.131 AC: 630 AN: 4822

European-Finnish (FIN) AF: 0.156 AC: 1649 AN: 10594

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0941 AC: 6397 AN: 67990

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.0843 Hom.: 75

Bravo AF: 0.0720

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

ClinVar submissions

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	-0.85
CADD	Benign	4.4
DANN	Benign	0.69
PhyloP100		-0.062
PromoterAI		0.056	Neutral
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: rs77058781; hg19: chr5-156886850;