chr7-86893030-G-A

Variant names:

• chr7-86893030-G-A
• rs1167836590
• NM_001142749.3:c.2756C>T

Variant summary

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

The NM_001142749.3(ELAPOR2):​c.2756C>T​(p.Ala919Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 1,586,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A919S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ELAPOR2 NM_001142749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76
• Publications: 2 publications found

Genes affected

ELAPOR2 (HGNC:21945): (endosome-lysosome associated apoptosis and autophagy regulator family member 2) Predicted to enable BMP receptor binding activity. Predicted to be involved in negative regulation of nervous system development; positive regulation of BMP signaling pathway; and positive regulation of epidermis development. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07460138).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142749.3. 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
	ELAPOR2	NM_001142749.3	MANE Select	c.2756C>T	p.Ala919Val	missense	Exon 20 of 22	NP_001136221.1	A8MWY0-1
	ELAPOR2	NM_001291990.1		c.2414C>T	p.Ala805Val	missense	Exon 20 of 22	NP_001278919.1	B4E116
	ELAPOR2	NM_152748.4		c.2255C>T	p.Ala752Val	missense	Exon 19 of 21	NP_689961.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAPOR2	ENST00000450689.7	TSL:5 MANE Select	c.2756C>T	p.Ala919Val	missense	Exon 20 of 22	ENSP00000413445.2	A8MWY0-1
	ELAPOR2	ENST00000971399.1		c.2831C>T	p.Ala944Val	missense	Exon 21 of 23	ENSP00000641458.1
	ELAPOR2	ENST00000860453.1		c.2591C>T	p.Ala864Val	missense	Exon 20 of 22	ENSP00000530512.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151682 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 225794 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 AF: 0.00000139 AC: 2 AN: 1434554 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 713260

African (AFR) AF: 0.00 AC: 0 AN: 30798

American (AMR) AF: 0.00 AC: 0 AN: 38824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 37860

South Asian (SAS) AF: 0.00 AC: 0 AN: 81266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102062

Other (OTH) AF: 0.00 AC: 0 AN: 59260

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151682 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74028

African (AFR) AF: 0.00 AC: 0 AN: 41298

American (AMR) AF: 0.000197 AC: 3 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67920

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	N
PhyloP100		2.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.055
Sift	Benign	0.20	T
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.053
MutPred		0.33		Gain of sheet (P = 0.0221)
MVP		0.22
MPC		0.22
ClinPred		0.29	T
GERP RS		6.0
Varity_R		0.080
gMVP		0.51
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1167836590; hg19: chr7-86522346;