4-145104331-T-C

Variant names:

• chr4-145104331-T-C
• rs17019887
• NM_002940.3:c.-27-55T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002940.3(ABCE1):​c.-27-55T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 693,298 control chromosomes in the GnomAD database, including 68 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 0.015 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (15 hom.)
• Consequence: ABCE1 NM_002940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• 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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2212/152300) while in subpopulation AFR AF = 0.0506 (2103/41568). AF 95% confidence interval is 0.0488. There are 53 homozygotes in GnomAd4. There are 1042 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2212 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002940.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCE1	NM_002940.3	MANE Select	c.-27-55T>C		intron	N/A	NP_002931.2
	ABCE1	NM_001040876.2		c.-24-58T>C		intron	N/A	NP_001035809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCE1	ENST00000296577.9	TSL:1 MANE Select	c.-27-55T>C		intron	N/A	ENSP00000296577.4
	ABCE1	ENST00000507193.5	TSL:1	n.-27-55T>C		intron	N/A	ENSP00000422068.1
	ABCE1	ENST00000502586.5	TSL:5	c.-24-58T>C		intron	N/A	ENSP00000421250.1

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2213 AN: 152182 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

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: 0.000103

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00145 AC: 782 AN: 540998 Hom.: 15 AF XY: 0.00121 AC XY: 341 AN XY: 281604

African (AFR) AF: 0.0465 AC: 593 AN: 12742

American (AMR) AF: 0.00277 AC: 48 AN: 17304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14616

East Asian (EAS) AF: 0.00 AC: 0 AN: 26944

South Asian (SAS) AF: 0.0000617 AC: 2 AN: 32410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38284

Middle Eastern (MID) AF: 0.000591 AC: 2 AN: 3382

European-Non Finnish (NFE) AF: 0.0000680 AC: 25 AN: 367664

Other (OTH) AF: 0.00405 AC: 112 AN: 27652

GnomAD4 genome AF: 0.0145 AC: 2212 AN: 152300 Hom.: 53 Cov.: 32 AF XY: 0.0140 AC XY: 1042 AN XY: 74478

African (AFR) AF: 0.0506 AC: 2103 AN: 41568

American (AMR) AF: 0.00549 AC: 84 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68016

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.0131 Hom.: 4

Bravo AF: 0.0167

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.67
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism

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: rs17019887; hg19: chr4-146025483;