chr4-145112254-G-A

Variant names:

• chr4-145112254-G-A
• rs35406092
• NM_002940.3:c.726G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_002940.3(ABCE1):​c.726G>A​(p.Glu242Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,435,060 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (11 hom., cov: 31)
  • Exomes 𝑓: 0.00057 (13 hom.)
• Consequence: ABCE1 NM_002940.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.18
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 4-145112254-G-A is Benign according to our data. Variant chr4-145112254-G-A is described in ClinVar as Benign. ClinVar VariationId is 714248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.18 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0062 (901/145406) while in subpopulation AFR AF = 0.0223 (875/39238). AF 95% confidence interval is 0.0211. There are 11 homozygotes in GnomAd4. There are 436 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 901 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCE1	NM_002940.3	c.726G>A	p.Glu242Glu	synonymous_variant	Exon 9 of 18	ENST00000296577.9	NP_002931.2
ABCE1	NM_001040876.2	c.726G>A	p.Glu242Glu	synonymous_variant	Exon 9 of 18		NP_001035809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCE1	ENST00000296577.9	c.726G>A	p.Glu242Glu	synonymous_variant	Exon 9 of 18	1	NM_002940.3	ENSP00000296577.4

Frequencies

GnomAD3 genomes AF: 0.00619 AC: 900 AN: 145318 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

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: 0.0000449

Gnomad OTH AF: 0.00251

GnomAD2 exomes AF: 0.00139 AC: 292 AN: 209926 AF XY: 0.00118

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.000199

GnomAD4 exome AF: 0.000571 AC: 737 AN: 1289654 Hom.: 13 Cov.: 30 AF XY: 0.000523 AC XY: 337 AN XY: 644746

African (AFR) AF: 0.0224 AC: 645 AN: 28778

American (AMR) AF: 0.000499 AC: 17 AN: 34096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23242

East Asian (EAS) AF: 0.00 AC: 0 AN: 37758

South Asian (SAS) AF: 0.0000665 AC: 5 AN: 75134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51750

Middle Eastern (MID) AF: 0.000818 AC: 4 AN: 4892

European-Non Finnish (NFE) AF: 0.00000612 AC: 6 AN: 979994

Other (OTH) AF: 0.00111 AC: 60 AN: 54010

GnomAD4 genome AF: 0.00620 AC: 901 AN: 145406 Hom.: 11 Cov.: 31 AF XY: 0.00619 AC XY: 436 AN XY: 70450

African (AFR) AF: 0.0223 AC: 875 AN: 39238

American (AMR) AF: 0.00125 AC: 18 AN: 14396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 4956

South Asian (SAS) AF: 0.00 AC: 0 AN: 4598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000449 AC: 3 AN: 66822

Other (OTH) AF: 0.00248 AC: 5 AN: 2014

Alfa AF: 0.00326 Hom.: 4

Bravo AF: 0.00644

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.5
DANN	Benign	0.95
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=81/19	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: rs35406092; hg19: chr4-146033406;