NM_001142749.3:c.2927C>T

Variant names:

• chr7-86891827-G-A
• rs140842262
• NM_001142749.3:c.2927C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001142749.3(ELAPOR2):​c.2927C>T​(p.Ala976Val) variant causes a missense change. The variant allele was found at a frequency of 0.000163 in 1,611,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: ELAPOR2 NM_001142749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.120017976).

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.2927C>T	p.Ala976Val	missense	Exon 21 of 22	NP_001136221.1	A8MWY0-1
	ELAPOR2	NM_001291990.1		c.2585C>T	p.Ala862Val	missense	Exon 21 of 22	NP_001278919.1	B4E116
	ELAPOR2	NM_152748.4		c.2426C>T	p.Ala809Val	missense	Exon 20 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.2927C>T	p.Ala976Val	missense	Exon 21 of 22	ENSP00000413445.2	A8MWY0-1
	ELAPOR2	ENST00000971399.1		c.3002C>T	p.Ala1001Val	missense	Exon 22 of 23	ENSP00000641458.1
	ELAPOR2	ENST00000860453.1		c.2762C>T	p.Ala921Val	missense	Exon 21 of 22	ENSP00000530512.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 151924 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000144 AC: 36 AN: 250048 AF XY: 0.000126

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000555

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000164 AC: 240 AN: 1459860 Hom.: 0 Cov.: 29 AF XY: 0.000164 AC XY: 119 AN XY: 726254

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.000180 AC: 8 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 86122

European-Finnish (FIN) AF: 0.000525 AC: 28 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.000180 AC: 200 AN: 1110764

Other (OTH) AF: 0.0000498 AC: 3 AN: 60270

GnomAD4 genome AF: 0.000151 AC: 23 AN: 151924 Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12 AN XY: 74192

African (AFR) AF: 0.0000483 AC: 2 AN: 41374

American (AMR) AF: 0.0000657 AC: 1 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000144 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.0000989 AC: 12

EpiCase AF: 0.0000549

EpiControl AF: 0.000179

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	0.20
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.18
Sift	Uncertain	0.027	D
Sift4G	Benign	0.13	T
Polyphen		0.92	P
Vest4		0.20
MVP		0.31
MPC		0.38
ClinPred		0.24	T
GERP RS		5.8
Varity_R		0.30
gMVP		0.30
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs140842262; hg19: chr7-86521143;