rs36114072

Positions:

• chr4-145118282-CTT-C
• chr4-145118282-CTT-CTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000296577.9(ABCE1):​c.922+873_922+874del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00824 in 145,036 control chromosomes in the GnomAD database, including 20 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0082 (20 hom., cov: 31)
• Consequence: ABCE1 ENST00000296577.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

Genes affected

ABCE1 (HGNC:69): (ATP binding cassette subfamily E member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the OABP subfamily. Alternatively referred to as the RNase L inhibitor, this protein functions to block the activity of ribonuclease L. Activation of ribonuclease L leads to inhibition of protein synthesis in the 2-5A/RNase L system, the central pathway for viral interferon action. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

OTUD4 (HGNC:24949): (OTU deubiquitinase 4) Alternatively spliced transcript variants have been found for this gene. The smaller protein isoform encoded by the shorter transcript variant is found only in HIV-1 infected cells. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00824 (1195/145036) while in subpopulation AFR AF= 0.0284 (1126/39602). AF 95% confidence interval is 0.0271. There are 20 homozygotes in gnomad4. There are 546 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1195 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCE1	NM_002940.3	c.922+873_922+874del		intron_variant		ENST00000296577.9	NP_002931.2
ABCE1	NM_001040876.2	c.922+873_922+874del		intron_variant			NP_001035809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCE1	ENST00000296577.9	c.922+873_922+874del		intron_variant		1	NM_002940.3	ENSP00000296577	P1

Frequencies

GnomAD3 genomes AF: 0.00825 AC: 1196 AN: 144954 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00241

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0229

Gnomad NFE AF: 0.000274

Gnomad OTH AF: 0.00501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00824 AC: 1195 AN: 145036 Hom.: 20 Cov.: 31 AF XY: 0.00774 AC XY: 546 AN XY: 70534

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.00241

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000274

Gnomad4 OTH AF: 0.00495

Alfa AF: 0.000937 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs36114072; hg19: chr4-146039434;