chr4-145107164-A-G

Variant names:

• chr4-145107164-A-G
• rs959304
• NM_002940.3:c.190-851A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002940.3(ABCE1):​c.190-851A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 152,176 control chromosomes in the GnomAD database, including 74,110 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.99 (74110 hom., cov: 31)
• Consequence: ABCE1 NM_002940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCE1	NM_002940.3	c.190-851A>G		intron_variant	Intron 3 of 17	ENST00000296577.9	NP_002931.2
ABCE1	NM_001040876.2	c.190-851A>G		intron_variant	Intron 3 of 17		NP_001035809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCE1	ENST00000296577.9	c.190-851A>G		intron_variant	Intron 3 of 17	1	NM_002940.3	ENSP00000296577.4

Frequencies

GnomAD3 genomes AF: 0.987 AC: 150049 AN: 152058 Hom.: 74062 Cov.: 31

Gnomad AFR AF: 0.954

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.991

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

GnomAD4 genome AF: 0.987 AC: 150153 AN: 152176 Hom.: 74110 Cov.: 31 AF XY: 0.987 AC XY: 73407 AN XY: 74378

African (AFR) AF: 0.954 AC: 39598 AN: 41514

American (AMR) AF: 0.996 AC: 15213 AN: 15274

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5177 AN: 5178

South Asian (SAS) AF: 1.00 AC: 4817 AN: 4818

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67964 AN: 67982

Other (OTH) AF: 0.991 AC: 2095 AN: 2114

Alfa AF: 0.995 Hom.: 3872

Bravo AF: 0.985

Asia WGS AF: 0.990 AC: 3442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.27
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs959304; hg19: chr4-146028316;