rs77372450

Variant names:

• chr5-157543136-A-C
• rs77372450
• NM_033274.5:c.252-5145T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-157543136-A-C
• chr5-157543136-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAM19	NM_033274.5	c.252-5145T>G		intron_variant	Intron 3 of 22	ENST00000257527.9	NP_150377.1
ADAM19	XM_047417858.1	c.252-5145T>G		intron_variant	Intron 3 of 21		XP_047273814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000257527.9	c.252-5145T>G		intron_variant	Intron 3 of 22	1	NM_033274.5	ENSP00000257527.5
ADAM19	ENST00000517905.1	c.252-5145T>G		intron_variant	Intron 3 of 21	5		ENSP00000428654.1
ADAM19	ENST00000517951.5	n.252-5145T>G		intron_variant	Intron 3 of 22	2		ENSP00000428376.1

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

African (AFR) AF: 0.0173 AC: 717 AN: 41486

American (AMR) AF: 0.0538 AC: 823 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 244 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4818

European-Finnish (FIN) AF: 0.0696 AC: 737 AN: 10594

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0666 AC: 4532 AN: 67998

Other (OTH) AF: 0.0683 AC: 144 AN: 2108

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
PhyloP100		-0.10
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: rs77372450; hg19: chr5-156970144;