NM_001974.5:c.1615A>T

Variant names:

• chr19-6919742-A-T
• rs461645
• NM_001974.5:c.1615A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001974.5(ADGRE1):​c.1615A>T​(p.Ile539Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 28)
• Consequence: ADGRE1 NM_001974.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 37 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.121869).

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.1615A>T	p.Ile539Phe	missense	Exon 13 of 21	NP_001965.3
	ADGRE1	NM_001256252.2		c.1459A>T	p.Ile487Phe	missense	Exon 12 of 20	NP_001243181.1	Q14246-3
	ADGRE1	NM_001256253.2		c.1615A>T	p.Ile539Phe	missense	Exon 13 of 20	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.1615A>T	p.Ile539Phe	missense	Exon 13 of 21	ENSP00000311545.3	Q14246-1
	ADGRE1	ENST00000250572.12	TSL:1	c.1615A>T	p.Ile539Phe	missense	Exon 13 of 20	ENSP00000250572.7	Q14246-2
	ADGRE1	ENST00000381404.8	TSL:2	c.1459A>T	p.Ile487Phe	missense	Exon 12 of 20	ENSP00000370811.4	Q14246-3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250662 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.63	T
PhyloP100		0.077
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.095
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.022	D
Polyphen		0.27	B
Vest4		0.26
MutPred		0.39		Loss of catalytic residue at P541 (P = 0.0423)
MVP		0.33
MPC		0.53
ClinPred		0.87	D
GERP RS		-0.14
Varity_R		0.24
gMVP		0.11
Mutation Taster		=95/5	polymorphism

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: rs461645; hg19: chr19-6919753;