4-145123265-C-T

Variant names:

• chr4-145123265-C-T
• rs34070877
• NM_002940.3:c.1425C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002940.3(ABCE1):​c.1425C>T​(p.Cys475Cys) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.17
• Publications: 3 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]

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

Our verdict: Benign. The variant received -21 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 VariationId is 769637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1883 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.1425C>T	p.Cys475Cys	synonymous	Exon 15 of 18	NP_002931.2
	ABCE1	NM_001040876.2		c.1425C>T	p.Cys475Cys	synonymous	Exon 15 of 18	NP_001035809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCE1	ENST00000296577.9	TSL:1 MANE Select	c.1425C>T	p.Cys475Cys	synonymous	Exon 15 of 18	ENSP00000296577.4
	ABCE1	ENST00000507193.5	TSL:1	n.*369C>T		non_coding_transcript_exon	Exon 16 of 19	ENSP00000422068.1
	ABCE1	ENST00000507193.5	TSL:1	n.*369C>T		3_prime_UTR	Exon 16 of 19	ENSP00000422068.1

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

GnomAD2 exomes AF: 0.00339 AC: 847 AN: 250058 AF XY: 0.00236

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 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

African (AFR) AF: 0.0410 AC: 1368 AN: 33356

American (AMR) AF: 0.00353 AC: 157 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.000921 AC: 24 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000256 AC: 22 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00617 AC: 34 AN: 5512

European-Non Finnish (NFE) AF: 0.000278 AC: 309 AN: 1111470

Other (OTH) AF: 0.00436 AC: 263 AN: 60290

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

African (AFR) AF: 0.0419 AC: 1738 AN: 41528

American (AMR) AF: 0.00549 AC: 84 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68006

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00626 Hom.: 10

Bravo AF: 0.0142

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.0
DANN	Benign	0.51
PhyloP100		1.2
Mutation Taster		=99/1	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: rs34070877; hg19: chr4-146044417;