chr10-50849248-T-C

Position:

• chr10-50849248-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014576.4(A1CF):​c.100-5126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,082 control chromosomes in the GnomAD database, including 4,677 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 0.23 (4677 hom., cov: 32)
• Consequence: A1CF NM_014576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A1CF	NM_014576.4	c.100-5126A>G		intron_variant		ENST00000373997.8	NP_055391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A1CF	ENST00000373997.8	c.100-5126A>G		intron_variant		1	NM_014576.4	ENSP00000363109	A1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34860 AN: 151964 Hom.: 4666 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.229 AC: 34883 AN: 152082 Hom.: 4677 Cov.: 32 AF XY: 0.232 AC XY: 17279 AN XY: 74328

Gnomad4 AFR AF: 0.0831

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.229

Alfa AF: 0.258 Hom.: 1086

Bravo AF: 0.221

Asia WGS AF: 0.352 AC: 1218 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs12570156; hg19: chr10-52609008;