19-6919742-ATT-GTC

Variant names:

• chr19-6919742-ATT-GTC
• NM_001974.5:c.1615_1617delATTinsGTC
• ADGRE1 p.Ile539Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001974.5(ADGRE1):​c.1615_1617delATTinsGTC​(p.Ile539Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I539F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 28)
• Consequence: ADGRE1 NM_001974.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 0 publications found

Genes affected

ADGRE1 (HGNC:3336): (adhesion G protein-coupled receptor E1) This gene encodes a protein that has a domain resembling seven transmembrane G protein-coupled hormone receptors (7TM receptors) at its C-terminus. The N-terminus of the encoded protein has six EGF-like modules, separated from the transmembrane segments by a serine/threonine-rich domain, a feature reminiscent of mucin-like, single-span, integral membrane glycoproteins with adhesive properties. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

LOC105372256 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001974.5. 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
	ADGRE1	NM_001974.5	MANE Select	c.1615_1617delATTinsGTC	p.Ile539Val	missense	N/A	NP_001965.3
	ADGRE1	NM_001256252.2		c.1459_1461delATTinsGTC	p.Ile487Val	missense	N/A	NP_001243181.1	Q14246-3
	ADGRE1	NM_001256253.2		c.1615_1617delATTinsGTC	p.Ile539Val	missense	N/A	NP_001243182.1	Q14246-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRE1	ENST00000312053.9	TSL:1 MANE Select	c.1615_1617delATTinsGTC	p.Ile539Val	missense	N/A	ENSP00000311545.3	Q14246-1
	ADGRE1	ENST00000250572.12	TSL:1	c.1615_1617delATTinsGTC	p.Ile539Val	missense	N/A	ENSP00000250572.7	Q14246-2
	ADGRE1	ENST00000381404.8	TSL:2	c.1459_1461delATTinsGTC	p.Ile487Val	missense	N/A	ENSP00000370811.4	Q14246-3

Frequencies

GnomAD3 genomes Cov.: 28

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

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.077

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-6919753;