5-157459811-G-C

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+197C>G 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 0.0797 in 152,086 control chromosomes in the GnomAD database, including 619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.080 (619 hom., cov: 32)
• Consequence: NIPAL4-DT NR_136205.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.440

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=-0.86).
• BP6: Variant 5-157459811-G-C is Benign according to our data. Variant chr5-157459811-G-C is described in ClinVar as [Benign]. Clinvar id is 1222176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPAL4-DT	NR_136205.1	n.93+197C>G		intron_variant, non_coding_transcript_variant
NIPAL4-DT	NR_136204.1	n.93+197C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM19	ENST00000517951.5	c.*1741+28454C>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12104 AN: 151968 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0804

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

GnomAD4 genome AF: 0.0797 AC: 12125 AN: 152086 Hom.: 619 Cov.: 32 AF XY: 0.0814 AC XY: 6052 AN XY: 74332

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.0785

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0273

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0846 Hom.: 72

Bravo AF: 0.0749

Asia WGS AF: 0.125 AC: 433 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.3
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76319946; hg19: chr5-156886819;