1-28237741-A-G

Variant names:

• chr1-28237741-A-G
• rs8559
• ENST00000465645.1:c.*1285A>G

Variant summary

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

The ENST00000465645.1(ATP5IF1):​c.*1285A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,612,382 control chromosomes in the GnomAD database, including 109,955 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 0.43 (16370 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93585 hom.)
• Consequence: ATP5IF1 ENST00000465645.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 40 publications found

Genes affected

ATP5IF1 (HGNC:871): (ATP synthase inhibitory factor subunit 1) Enables several functions, including ATPase binding activity; angiostatin binding activity; and mitochondrial proton-transporting ATP synthase complex binding activity. Involved in several processes, including mitochondrial depolarization; negative regulation of ATPase activity; and regulation of protein targeting to mitochondrion. Located in cell surface and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465645.1. 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
	ATP5IF1	NM_016311.5	MANE Select	c.180-96A>G		intron	N/A	NP_057395.1
	ATP5IF1	NM_178191.3		c.*1285A>G		3_prime_UTR	Exon 2 of 2	NP_835498.1
	ATP5IF1	NM_178190.3		c.180-20A>G		intron	N/A	NP_835497.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5IF1	ENST00000465645.1	TSL:1	c.*1285A>G		3_prime_UTR	Exon 2 of 2	ENSP00000437337.1
	ATP5IF1	ENST00000335514.10	TSL:1 MANE Select	c.180-96A>G		intron	N/A	ENSP00000335203.5
	ATP5IF1	ENST00000468425.2	TSL:2	c.179+1289A>G		intron	N/A	ENSP00000435341.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65914 AN: 152000 Hom.: 16340 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.421

GnomAD2 exomes AF: 0.335 AC: 83219 AN: 248536 AF XY: 0.330

Gnomad AFR exome AF: 0.688

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.0985

Gnomad FIN exome AF: 0.329

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.349 AC: 509634 AN: 1460264 Hom.: 93585 Cov.: 37 AF XY: 0.347 AC XY: 251862 AN XY: 726340

African (AFR) AF: 0.697 AC: 23293 AN: 33426

American (AMR) AF: 0.274 AC: 12185 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 10405 AN: 26108

East Asian (EAS) AF: 0.0957 AC: 3798 AN: 39676

South Asian (SAS) AF: 0.262 AC: 22552 AN: 86132

European-Finnish (FIN) AF: 0.329 AC: 17575 AN: 53356

Middle Eastern (MID) AF: 0.405 AC: 2336 AN: 5764

European-Non Finnish (NFE) AF: 0.356 AC: 395662 AN: 1110906

Other (OTH) AF: 0.362 AC: 21828 AN: 60352

GnomAD4 genome AF: 0.434 AC: 66004 AN: 152118 Hom.: 16370 Cov.: 32 AF XY: 0.427 AC XY: 31728 AN XY: 74360

African (AFR) AF: 0.681 AC: 28260 AN: 41494

American (AMR) AF: 0.343 AC: 5237 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1403 AN: 3472

East Asian (EAS) AF: 0.0993 AC: 515 AN: 5186

South Asian (SAS) AF: 0.242 AC: 1165 AN: 4818

European-Finnish (FIN) AF: 0.332 AC: 3514 AN: 10580

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24461 AN: 67972

Other (OTH) AF: 0.419 AC: 885 AN: 2112

Alfa AF: 0.381 Hom.: 40144

Bravo AF: 0.446

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.70
PhyloP100		-0.30
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: rs8559; hg19: chr1-28564252; COSMIC: COSV55281415; COSMIC: COSV55281415;