4-145110451-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002940.3(ABCE1):c.613+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,610,802 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (15 hom.)
• Consequence: ABCE1 NM_002940.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006002
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.716

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-145110451-G-T is Benign according to our data. Variant chr4-145110451-G-T is described in ClinVar as [Benign]. Clinvar id is 709737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00656 (997/152088) while in subpopulation AFR AF= 0.023 (956/41492). AF 95% confidence interval is 0.0218. There are 13 homozygotes in gnomad4. There are 487 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 993 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCE1	NM_002940.3	c.613+7G>T		splice_region_variant, intron_variant		ENST00000296577.9
ABCE1	NM_001040876.2	c.613+7G>T		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCE1	ENST00000296577.9	c.613+7G>T		splice_region_variant, intron_variant		1	NM_002940.3	P1

Frequencies

GnomAD3 genomes AF: 0.00653 AC: 993 AN: 151970 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00625

GnomAD3 exomes AF: 0.00177 AC: 445 AN: 250752 Hom.: 8 AF XY: 0.00130 AC XY: 176 AN XY: 135538

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.000667

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.000677 AC: 987 AN: 1458714 Hom.: 15 Cov.: 32 AF XY: 0.000562 AC XY: 408 AN XY: 725686

Gnomad4 AFR exome AF: 0.0252

Gnomad4 AMR exome AF: 0.000851

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000931

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.00135

GnomAD4 genome AF: 0.00656 AC: 997 AN: 152088 Hom.: 13 Cov.: 32 AF XY: 0.00655 AC XY: 487 AN XY: 74380

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00618

Alfa AF: 0.00366 Hom.: 5

Bravo AF: 0.00760

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

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

Jan 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	8.9
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000060
dbscSNV1_RF	Benign	0.0
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: rs111590771; hg19: chr4-146031603;