rs2277027

chr5-157505368-A-C

Variant summary

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

The NM_033274.5(ADAM19):c.1130+301T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,876 control chromosomes in the GnomAD database, including 14,427 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 0.42 (14427 hom., cov: 31)
• Consequence: ADAM19 NM_033274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM19	NM_033274.5	c.1130+301T>G		intron_variant		ENST00000257527.9
ADAM19	XM_047417858.1	c.1130+301T>G		intron_variant
ADAM19	XM_047417859.1	c.329+301T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM19	ENST00000257527.9	c.1130+301T>G		intron_variant		1	NM_033274.5	P1
ADAM19	ENST00000517905.1	c.1130+301T>G		intron_variant		5
ADAM19	ENST00000517951.5	c.*321+301T>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63498 AN: 151758 Hom.: 14389 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.419 AC: 63593 AN: 151876 Hom.: 14427 Cov.: 31 AF XY: 0.420 AC XY: 31154 AN XY: 74210

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.430

Alfa AF: 0.354 Hom.: 21368

Bravo AF: 0.429

Asia WGS AF: 0.314 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.56
Dann	Benign	0.73

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: rs2277027; hg19: chr5-156932376; COSMIC: COSV57425346; COSMIC: COSV57425346;