5-157518140-T-C

Position:

• chr5-157518140-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_033274.5(ADAM19):​c.666+683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 151,902 control chromosomes in the GnomAD database, including 437 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 0.070 (437 hom., cov: 31)
• Consequence: ADAM19 NM_033274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM19	NM_033274.5	c.666+683A>G		intron_variant		ENST00000257527.9	NP_150377.1
ADAM19	XM_047417858.1	c.666+683A>G		intron_variant			XP_047273814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000257527.9	c.666+683A>G		intron_variant		1	NM_033274.5	ENSP00000257527	P1
ADAM19	ENST00000517905.1	c.666+683A>G		intron_variant		5		ENSP00000428654
ADAM19	ENST00000517951.5	c.666+683A>G		intron_variant, NMD_transcript_variant		2		ENSP00000428376

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10683 AN: 151786 Hom.: 437 Cov.: 31

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0724

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0704 AC: 10698 AN: 151902 Hom.: 437 Cov.: 31 AF XY: 0.0694 AC XY: 5156 AN XY: 74250

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.0667

Gnomad4 ASJ AF: 0.0724

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0722

Gnomad4 NFE AF: 0.0684

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0704 Hom.: 81

Bravo AF: 0.0719

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	16
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs58873874; hg19: chr5-156945148;