5-157494947-A-G

Position:

• chr5-157494947-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033274.5(ADAM19):​c.1595-152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 583,272 control chromosomes in the GnomAD database, including 4,657 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 0.11 (1032 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3625 hom.)
• Consequence: ADAM19 NM_033274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM19	NM_033274.5	c.1595-152T>C		intron_variant		ENST00000257527.9	NP_150377.1
ADAM19	XM_047417858.1	c.1595-152T>C		intron_variant			XP_047273814.1
ADAM19	XM_047417859.1	c.794-152T>C		intron_variant			XP_047273815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000257527.9	c.1595-152T>C		intron_variant		1	NM_033274.5	ENSP00000257527	P1
ADAM19	ENST00000517374.5	c.307-152T>C		intron_variant		1		ENSP00000431027
ADAM19	ENST00000517905.1	c.1595-152T>C		intron_variant		5		ENSP00000428654
ADAM19	ENST00000517951.5	c.*786-152T>C		intron_variant, NMD_transcript_variant		2		ENSP00000428376

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16240 AN: 151736 Hom.: 1031 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.120 AC: 51623 AN: 431416 Hom.: 3625 AF XY: 0.121 AC XY: 27641 AN XY: 228996

Gnomad4 AFR exome AF: 0.0533

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.107 AC: 16243 AN: 151856 Hom.: 1032 Cov.: 32 AF XY: 0.113 AC XY: 8370 AN XY: 74220

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.104

Alfa AF: 0.105 Hom.: 798

Bravo AF: 0.108

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11466782; hg19: chr5-156921955; COSMIC: COSV57425272;