5-157459885-C-T

Position:

• chr5-157459885-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+123G>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 0.0872 in 398,866 control chromosomes in the GnomAD database, including 1,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.079 (613 hom., cov: 32)
  • Exomes 𝑓: 0.092 (1164 hom.)
• Consequence: NIPAL4-DT NR_136205.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.163

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=-0.85).
• BP6: Variant 5-157459885-C-T is Benign according to our data. Variant chr5-157459885-C-T is described in ClinVar as [Benign]. Clinvar id is 1267802.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	Protein	UniProt
NIPAL4-DT	NR_136205.1	n.93+123G>A		intron_variant, non_coding_transcript_variant
NIPAL4-DT	NR_136204.1	n.93+123G>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+28380G>A		intron_variant, NMD_transcript_variant		2		ENSP00000428376

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12026 AN: 152142 Hom.: 612 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0799

GnomAD4 exome AF: 0.0923 AC: 22759 AN: 246606 Hom.: 1164 AF XY: 0.0932 AC XY: 11656 AN XY: 125028

Gnomad4 AFR exome AF: 0.0325

Gnomad4 AMR exome AF: 0.0715

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.0369

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.0935

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0905

GnomAD4 genome AF: 0.0791 AC: 12040 AN: 152260 Hom.: 613 Cov.: 32 AF XY: 0.0808 AC XY: 6011 AN XY: 74436

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0270

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0966

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0843

Alfa AF: 0.0779 Hom.: 75

Bravo AF: 0.0740

Asia WGS AF: 0.124 AC: 430 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	-0.85
CADD	Benign	5.4
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs80136550; hg19: chr5-156886893;