chr7-86880476-T-C

Variant names:

• chr7-86880476-T-C
• rs376938495
• NM_001142749.3:c.3085A>G

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.3085A>G​(p.Ile1029Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000454 in 1,608,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: ELAPOR2 NM_001142749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43
• Publications: 0 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=0.09546581).

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.3085A>G	p.Ile1029Val	missense	Exon 22 of 22	NP_001136221.1	A8MWY0-1
	ELAPOR2	NM_001291990.1		c.2743A>G	p.Ile915Val	missense	Exon 22 of 22	NP_001278919.1	B4E116
	ELAPOR2	NM_152748.4		c.2584A>G	p.Ile862Val	missense	Exon 21 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.3085A>G	p.Ile1029Val	missense	Exon 22 of 22	ENSP00000413445.2	A8MWY0-1
	ELAPOR2	ENST00000971399.1		c.3160A>G	p.Ile1054Val	missense	Exon 23 of 23	ENSP00000641458.1
	ELAPOR2	ENST00000860453.1		c.2920A>G	p.Ile974Val	missense	Exon 22 of 22	ENSP00000530512.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152048 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.0000882

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.0000440 AC: 11 AN: 250042 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000426 AC: 62 AN: 1456002 Hom.: 0 Cov.: 27 AF XY: 0.0000455 AC XY: 33 AN XY: 724832

African (AFR) AF: 0.0000300 AC: 1 AN: 33368

American (AMR) AF: 0.0000895 AC: 4 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000434 AC: 48 AN: 1106822

Other (OTH) AF: 0.000133 AC: 8 AN: 60208

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152048 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74256

African (AFR) AF: 0.0000242 AC: 1 AN: 41388

American (AMR) AF: 0.0000656 AC: 1 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.00144 AC: 3 AN: 2082

Alfa AF: 0.0000966 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

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	0.097
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.084
Sift	Uncertain	0.022	D
Sift4G	Benign	0.23	T
Polyphen		0.41	B
Vest4		0.45
MVP		0.15
MPC		0.22
ClinPred		0.075	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.042
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs376938495; hg19: chr7-86509792;