chr5-157525400-C-G

Position:

• chr5-157525400-C-G

Variant summary

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

The NM_033274.5(ADAM19):​c.408-5369G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,028 control chromosomes in the GnomAD database, including 8,011 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 0.31 (8011 hom., cov: 32)
• Consequence: ADAM19 NM_033274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM19	NM_033274.5	c.408-5369G>C		intron_variant		ENST00000257527.9	NP_150377.1
ADAM19	XM_047417858.1	c.408-5369G>C		intron_variant			XP_047273814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000257527.9	c.408-5369G>C		intron_variant		1	NM_033274.5	ENSP00000257527.5
ADAM19	ENST00000517905.1	c.408-5369G>C		intron_variant		5		ENSP00000428654.1
ADAM19	ENST00000517951.5	n.408-5369G>C		intron_variant		2		ENSP00000428376.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46949 AN: 151910 Hom.: 7996 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.309 AC: 46991 AN: 152028 Hom.: 8011 Cov.: 32 AF XY: 0.312 AC XY: 23157 AN XY: 74296

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.324

Alfa AF: 0.140 Hom.: 243

Bravo AF: 0.318

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.52

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: rs7721142; hg19: chr5-156952408; COSMIC: COSV57425584;