rs2359245

Variant names:

• chr1-109194468-G-A
• rs2359245
• NM_020775.5:c.1995G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020775.5(ELAPOR1):​c.1995G>A​(p.Pro665Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,611,922 control chromosomes in the GnomAD database, including 476,261 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P665P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.67 (36875 hom., cov: 33)
  • Exomes 𝑓: 0.77 (439386 hom.)
• Consequence: ELAPOR1 NM_020775.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 22 publications found

Genes affected

ELAPOR1 (HGNC:29618): (endosome-lysosome associated apoptosis and autophagy regulator 1) Expression of this gene is induced by estrogen and the encoded protein has been characterized as a transmembrane protein. The encoded protein has been found in to correlate with survival in certain carcinomas (PMID: 21102415) and may be important for cellular response to stress (PMID: 21072319). Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-1.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020775.5. 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
	ELAPOR1	NM_020775.5	MANE Select	c.1995G>A	p.Pro665Pro	synonymous	Exon 15 of 22	NP_065826.3
	ELAPOR1	NM_001267048.2		c.1734G>A	p.Pro578Pro	synonymous	Exon 13 of 20	NP_001253977.2	Q6UXG2-3
	ELAPOR1	NM_001284352.2		c.1689G>A	p.Pro563Pro	synonymous	Exon 14 of 21	NP_001271281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAPOR1	ENST00000369939.8	TSL:5 MANE Select	c.1995G>A	p.Pro665Pro	synonymous	Exon 15 of 22	ENSP00000358955.3	Q6UXG2-1
	ELAPOR1	ENST00000529753.5	TSL:1	c.1734G>A	p.Pro578Pro	synonymous	Exon 13 of 20	ENSP00000434595.1	Q6UXG2-3
	ELAPOR1	ENST00000369936.2	TSL:1	n.1152G>A		non_coding_transcript_exon	Exon 7 of 14

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101773 AN: 151986 Hom.: 36857 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.665

GnomAD2 exomes AF: 0.784 AC: 197052 AN: 251430 AF XY: 0.789

Gnomad AFR exome AF: 0.364

Gnomad AMR exome AF: 0.852

Gnomad ASJ exome AF: 0.705

Gnomad EAS exome AF: 0.971

Gnomad FIN exome AF: 0.840

Gnomad NFE exome AF: 0.766

Gnomad OTH exome AF: 0.773

GnomAD4 exome AF: 0.771 AC: 1125475 AN: 1459818 Hom.: 439386 Cov.: 52 AF XY: 0.774 AC XY: 562418 AN XY: 726378

African (AFR) AF: 0.349 AC: 11681 AN: 33428

American (AMR) AF: 0.843 AC: 37690 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 18553 AN: 26120

East Asian (EAS) AF: 0.979 AC: 38861 AN: 39700

South Asian (SAS) AF: 0.868 AC: 74854 AN: 86228

European-Finnish (FIN) AF: 0.839 AC: 44780 AN: 53404

Middle Eastern (MID) AF: 0.659 AC: 3800 AN: 5762

European-Non Finnish (NFE) AF: 0.766 AC: 850088 AN: 1110138

Other (OTH) AF: 0.749 AC: 45168 AN: 60320

GnomAD4 genome AF: 0.669 AC: 101822 AN: 152104 Hom.: 36875 Cov.: 33 AF XY: 0.679 AC XY: 50454 AN XY: 74356

African (AFR) AF: 0.371 AC: 15383 AN: 41446

American (AMR) AF: 0.753 AC: 11505 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2424 AN: 3466

East Asian (EAS) AF: 0.972 AC: 5015 AN: 5158

South Asian (SAS) AF: 0.877 AC: 4235 AN: 4830

European-Finnish (FIN) AF: 0.840 AC: 8898 AN: 10588

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52125 AN: 68016

Other (OTH) AF: 0.668 AC: 1413 AN: 2116

Alfa AF: 0.729 Hom.: 115305

Bravo AF: 0.650

Asia WGS AF: 0.880 AC: 3059 AN: 3478

EpiCase AF: 0.753

EpiControl AF: 0.747

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.038
DANN	Benign	0.62
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs2359245; hg19: chr1-109737090; COSMIC: COSV108205956; COSMIC: COSV108205956;