rs11744671

Positions:

• chr5-157494223-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM19	NM_033274.5	c.1703+464A>G		intron_variant		ENST00000257527.9	NP_150377.1
ADAM19	XM_047417858.1	c.1703+464A>G		intron_variant			XP_047273814.1
ADAM19	XM_047417859.1	c.902+464A>G		intron_variant			XP_047273815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM19	ENST00000257527.9	c.1703+464A>G		intron_variant		1	NM_033274.5	ENSP00000257527	P1
ADAM19	ENST00000517374.5	c.415+464A>G		intron_variant		1		ENSP00000431027
ADAM19	ENST00000517905.1	c.1703+464A>G		intron_variant		5		ENSP00000428654
ADAM19	ENST00000517951.5	c.*894+464A>G		intron_variant, NMD_transcript_variant		2		ENSP00000428376

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

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.0634

Gnomad4 ASJ AF: 0.0715

Gnomad4 EAS AF: 0.000974

Gnomad4 SAS AF: 0.0165

Gnomad4 FIN AF: 0.0811

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0558 Hom.: 25

Bravo AF: 0.0487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.53

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: rs11744671; hg19: chr5-156921231;