5-157459690-C-T

Position:

• chr5-157459690-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_136205.1(NIPAL4-DT):​n.93+318G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 150,810 control chromosomes in the GnomAD database, including 10,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (10879 hom., cov: 30)
• Consequence: NIPAL4-DT NR_136205.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

Genes affected

NIPAL4-DT (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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-157459690-C-T is Benign according to our data. Variant chr5-157459690-C-T is described in ClinVar as [Benign]. Clinvar id is 1276066.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPAL4-DT	NR_136205.1	n.93+318G>A		intron_variant, non_coding_transcript_variant
NIPAL4-DT	NR_136204.1	n.93+318G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000517951.5	c.*1741+28575G>A		intron_variant, NMD_transcript_variant		2		ENSP00000428376

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56364 AN: 150692 Hom.: 10863 Cov.: 30

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.374 AC: 56412 AN: 150810 Hom.: 10879 Cov.: 30 AF XY: 0.378 AC XY: 27789 AN XY: 73544

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.375

Alfa AF: 0.354 Hom.: 1210

Bravo AF: 0.370

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2098670; hg19: chr5-156886698;