rs34070877

chr4-145123265-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002940.3(ABCE1):c.1425C>T(p.Cys475=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,612,460 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (42 hom.)
• Consequence: ABCE1 NM_002940.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 4-145123265-C-T is Benign according to our data. Variant chr4-145123265-C-T is described in ClinVar as [Benign]. Clinvar id is 769637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1883/152228) while in subpopulation AFR AF= 0.0419 (1738/41528). AF 95% confidence interval is 0.0402. There are 42 homozygotes in gnomad4. There are 856 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1863 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCE1	NM_002940.3	c.1425C>T	p.Cys475=	synonymous_variant	15/18	ENST00000296577.9
ABCE1	NM_001040876.2	c.1425C>T	p.Cys475=	synonymous_variant	15/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCE1	ENST00000296577.9	c.1425C>T	p.Cys475=	synonymous_variant	15/18	1	NM_002940.3	P1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1863 AN: 152110 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00339 AC: 847 AN: 250058 Hom.: 13 AF XY: 0.00236 AC XY: 319 AN XY: 135196

Gnomad AFR exome AF: 0.0412

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000263

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00149 AC: 2177 AN: 1460232 Hom.: 42 Cov.: 31 AF XY: 0.00133 AC XY: 968 AN XY: 726390

Gnomad4 AFR exome AF: 0.0410

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.000921

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000256

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000278

Gnomad4 OTH exome AF: 0.00436

GnomAD4 genome AF: 0.0124 AC: 1883 AN: 152228 Hom.: 42 Cov.: 32 AF XY: 0.0115 AC XY: 856 AN XY: 74416

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00626 Hom.: 10

Bravo AF: 0.0142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.0
Dann	Benign	0.51

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: rs34070877; hg19: chr4-146044417;