chr5-157494223-T-C

Variant names:

• chr5-157494223-T-C
• rs11744671
• NM_033274.5:c.1703+464A>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.1703+464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 151,360 control chromosomes in the GnomAD database, including 268 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 0.051 (268 hom., cov: 32)
• Consequence: ADAM19 NM_033274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033274.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	NM_033274.5	MANE Select	c.1703+464A>G		intron	N/A	NP_150377.1	Q9H013-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	ENST00000257527.9	TSL:1 MANE Select	c.1703+464A>G		intron	N/A	ENSP00000257527.5	Q9H013-2
	ADAM19	ENST00000517374.5	TSL:1	c.413+464A>G		intron	N/A	ENSP00000431027.1	H0YC66
	ADAM19	ENST00000517905.1	TSL:5	c.1703+464A>G		intron	N/A	ENSP00000428654.1	Q9H013-1

Frequencies

GnomAD3 genomes AF: 0.0507 AC: 7661 AN: 151242 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.000972

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0731

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

GnomAD4 genome AF: 0.0506 AC: 7662 AN: 151360 Hom.: 268 Cov.: 32 AF XY: 0.0509 AC XY: 3763 AN XY: 73968

African (AFR) AF: 0.0120 AC: 493 AN: 41250

American (AMR) AF: 0.0634 AC: 963 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 247 AN: 3456

East Asian (EAS) AF: 0.000974 AC: 5 AN: 5132

South Asian (SAS) AF: 0.0165 AC: 79 AN: 4796

European-Finnish (FIN) AF: 0.0811 AC: 850 AN: 10480

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4755 AN: 67748

Other (OTH) AF: 0.0724 AC: 152 AN: 2100

Alfa AF: 0.0558 Hom.: 25

Bravo AF: 0.0487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-0.53
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: rs11744671; hg19: chr5-156921231;