5-157574727-T-G

Variant names:

• chr5-157574727-T-G
• rs6890282
• NM_033274.5:c.94+876A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033274.5(ADAM19):​c.94+876A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,962 control chromosomes in the GnomAD database, including 11,177 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 0.35 (11177 hom., cov: 32)
• Consequence: ADAM19 NM_033274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 4 publications found

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]

ENSG00000253519 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM19	NM_033274.5	c.94+876A>C		intron_variant	Intron 1 of 22	ENST00000257527.9	NP_150377.1
ADAM19	XM_047417858.1	c.94+876A>C		intron_variant	Intron 1 of 21		XP_047273814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000257527.9	c.94+876A>C		intron_variant	Intron 1 of 22	1	NM_033274.5	ENSP00000257527.5

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53152 AN: 151844 Hom.: 11160 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.350 AC: 53213 AN: 151962 Hom.: 11177 Cov.: 32 AF XY: 0.343 AC XY: 25471 AN XY: 74272

African (AFR) AF: 0.578 AC: 23918 AN: 41396

American (AMR) AF: 0.239 AC: 3655 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1443 AN: 3470

East Asian (EAS) AF: 0.0619 AC: 319 AN: 5152

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4814

European-Finnish (FIN) AF: 0.234 AC: 2472 AN: 10576

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19071 AN: 67962

Other (OTH) AF: 0.376 AC: 792 AN: 2104

Alfa AF: 0.247 Hom.: 1019

Bravo AF: 0.359

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.3
DANN	Benign	0.38
PhyloP100		-0.090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6890282; hg19: chr5-157001735; COSMIC: COSV57426200; COSMIC: COSV57426200;