chr10-50806818-G-T

Variant names:

• chr10-50806818-G-T
• rs923766063
• NM_014576.4:c.1672C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014576.4(A1CF):​c.1672C>A​(p.Leu558Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: A1CF NM_014576.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65
• Publications: 0 publications found

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]

ASAH2B (HGNC:23456): (N-acylsphingosine amidohydrolase 2B) Predicted to enable N-acylsphingosine amidohydrolase activity. Predicted to be involved in ceramide catabolic process; long-chain fatty acid biosynthetic process; and sphingosine biosynthetic process. Predicted to be active in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21466658).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014576.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	A1CF	NM_014576.4	MANE Select	c.1672C>A	p.Leu558Ile	missense	Exon 13 of 13	NP_055391.2
	A1CF	NM_001198819.2		c.1720C>A	p.Leu574Ile	missense	Exon 15 of 15	NP_001185748.1	F8W9F8
	A1CF	NM_001198820.2		c.1696C>A	p.Leu566Ile	missense	Exon 14 of 14	NP_001185749.1	Q9NQ94-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	A1CF	ENST00000373997.8	TSL:1 MANE Select	c.1672C>A	p.Leu558Ile	missense	Exon 13 of 13	ENSP00000363109.3	Q9NQ94-2
	A1CF	ENST00000373993.6	TSL:1	c.1696C>A	p.Leu566Ile	missense	Exon 12 of 12	ENSP00000363105.1	Q9NQ94-1
	A1CF	ENST00000855032.1		c.1750C>A	p.Leu584Ile	missense	Exon 15 of 15	ENSP00000525091.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461420 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727010

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111722

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.078
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.39	T
Polyphen		1.0	D
Vest4		0.31
MutPred		0.22		Gain of methylation at K561 (P = 0.0735)
MVP		0.21
MPC		0.58
ClinPred		0.71	D
GERP RS		4.8
Varity_R		0.16
gMVP		0.40
Mutation Taster		=81/19	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: rs923766063; hg19: chr10-52566578;