4-145110244-G-A

Position:

• chr4-145110244-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002940.3(ABCE1):​c.543+4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000723 in 1,597,196 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0039 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (5 hom.)
• Consequence: ABCE1 NM_002940.3 splice_region, intron
• Scores: Splicing: ADA: 0.00009785
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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]

ABCE1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BS2: High AC in GnomAd4 at 593 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCE1	NM_002940.3	c.543+4G>A		splice_region_variant, intron_variant		ENST00000296577.9	NP_002931.2
ABCE1	NM_001040876.2	c.543+4G>A		splice_region_variant, intron_variant			NP_001035809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCE1	ENST00000296577.9	c.543+4G>A		splice_region_variant, intron_variant		1	NM_002940.3	ENSP00000296577.4

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 590 AN: 151900 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000930 AC: 219 AN: 235362 Hom.: 1 AF XY: 0.000747 AC XY: 95 AN XY: 127108

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.000263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000578

Gnomad SAS exome AF: 0.0000377

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000640

Gnomad OTH exome AF: 0.000178

GnomAD4 exome AF: 0.000389 AC: 562 AN: 1445178 Hom.: 5 Cov.: 33 AF XY: 0.000341 AC XY: 245 AN XY: 718304

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.000421

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.0000975

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000298

Gnomad4 OTH exome AF: 0.000671

GnomAD4 genome AF: 0.00390 AC: 593 AN: 152018 Hom.: 1 Cov.: 32 AF XY: 0.00375 AC XY: 279 AN XY: 74310

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000942 Hom.: 2

Bravo AF: 0.00435

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000098
dbscSNV1_RF	Benign	0.052
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: rs35207405; hg19: chr4-146031396;