rs11740562

chr5-157515277-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.667-1772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 152,278 control chromosomes in the GnomAD database, including 441 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 (441 hom., cov: 32)
• Consequence: ADAM19 NM_033274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.088 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM19	NM_033274.5	c.667-1772T>C		intron_variant		ENST00000257527.9
ADAM19	XM_047417858.1	c.667-1772T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM19	ENST00000257527.9	c.667-1772T>C		intron_variant		1	NM_033274.5	P1
ADAM19	ENST00000517905.1	c.667-1772T>C		intron_variant		5
ADAM19	ENST00000517951.5	c.667-1772T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10570 AN: 152160 Hom.: 440 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0658

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0696 AC: 10591 AN: 152278 Hom.: 441 Cov.: 32 AF XY: 0.0688 AC XY: 5124 AN XY: 74452

Gnomad4 AFR AF: 0.0904

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0713

Gnomad4 NFE AF: 0.0658

Gnomad4 OTH AF: 0.0808

Alfa AF: 0.0633 Hom.: 443

Bravo AF: 0.0714

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	5.2
Dann	Benign	0.77

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: rs11740562; hg19: chr5-156942285;