rs77372450

chr5-157543136-A-Cchr5-157543136-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.252-5145T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 152,146 control chromosomes in the GnomAD database, including 248 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 0.049 (248 hom., cov: 33)
• Consequence: ADAM19 NM_033274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM19	NM_033274.5	c.252-5145T>G		intron_variant		ENST00000257527.9
ADAM19	XM_047417858.1	c.252-5145T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM19	ENST00000257527.9	c.252-5145T>G		intron_variant		1	NM_033274.5	P1
ADAM19	ENST00000517905.1	c.252-5145T>G		intron_variant		5
ADAM19	ENST00000517951.5	c.252-5145T>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7398 AN: 152028 Hom.: 248 Cov.: 33

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0690

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

GnomAD4 genome AF: 0.0486 AC: 7397 AN: 152146 Hom.: 248 Cov.: 33 AF XY: 0.0483 AC XY: 3594 AN XY: 74390

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.0538

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.0696

Gnomad4 NFE AF: 0.0666

Gnomad4 OTH AF: 0.0683

Alfa AF: 0.0292 Hom.: 14

Bravo AF: 0.0471

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.27
Dann	Benign	0.60

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: rs77372450; hg19: chr5-156970144;