rs10994860

Positions:

• chr10-50885664-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000395489.7(A1CF):​c.-389G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.184 in 152,084 control chromosomes in the GnomAD database, including 2,735 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 0.18 (2735 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: A1CF ENST00000395489.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.92

Genes affected

A1CF (HGNC:24086): (APOBEC1 complementation factor) Mammalian apolipoprotein B mRNA undergoes site-specific C to U deamination, which is mediated by a multi-component enzyme complex containing a minimal core composed of APOBEC-1 and a complementation factor encoded by this gene. The gene product has three non-identical RNA recognition motifs and belongs to the hnRNP R family of RNA-binding proteins. It has been proposed that this complementation factor functions as an RNA-binding subunit and docks APOBEC-1 to deaminate the upstream cytidine. Studies suggest that the protein may also be involved in other RNA editing or RNA processing events. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A1CF	NM_014576.4			upstream_gene_variant		ENST00000373997.8	NP_055391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A1CF	ENST00000373997.8			upstream_gene_variant		1	NM_014576.4	ENSP00000363109	A1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27981 AN: 151966 Hom.: 2728 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.175

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 AFR exome AF: 0.00

GnomAD4 genome AF: 0.184 AC: 28008 AN: 152084 Hom.: 2735 Cov.: 32 AF XY: 0.187 AC XY: 13885 AN XY: 74344

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0459

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.181

Alfa AF: 0.173 Hom.: 2278

Bravo AF: 0.173

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10994860; hg19: chr10-52645424; COSMIC: COSV105000370;