10-50814012-C-T

Position:

• chr10-50814012-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014576.4(A1CF):​c.1168G>A​(p.Gly390Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00773 in 1,613,676 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (57 hom.)
• Consequence: A1CF NM_014576.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.65

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

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010407597).
• BP6: Variant 10-50814012-C-T is Benign according to our data. Variant chr10-50814012-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A1CF	NM_014576.4	c.1168G>A	p.Gly390Ser	missense_variant	10/13	ENST00000373997.8	NP_055391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A1CF	ENST00000373997.8	c.1168G>A	p.Gly390Ser	missense_variant	10/13	1	NM_014576.4	ENSP00000363109	A1

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 894 AN: 152074 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00897

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00925

Gnomad OTH AF: 0.00912

GnomAD3 exomes AF: 0.00525 AC: 1317 AN: 250812 Hom.: 10 AF XY: 0.00516 AC XY: 699 AN XY: 135516

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00527

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00887

Gnomad OTH exome AF: 0.00572

GnomAD4 exome AF: 0.00793 AC: 11587 AN: 1461484 Hom.: 57 Cov.: 31 AF XY: 0.00772 AC XY: 5612 AN XY: 727074

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.00573

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.00152

Gnomad4 NFE exome AF: 0.00961

Gnomad4 OTH exome AF: 0.00676

GnomAD4 genome AF: 0.00587 AC: 894 AN: 152192 Hom.: 1 Cov.: 32 AF XY: 0.00544 AC XY: 405 AN XY: 74414

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00896

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00925

Gnomad4 OTH AF: 0.00902

Alfa AF: 0.00816 Hom.: 10

Bravo AF: 0.00634

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00826 AC: 71

ExAC AF: 0.00532 AC: 646

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00911

EpiControl AF: 0.00872

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	.;.;.;.;T;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	.;T;T;T;T;.;.
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.010	T;T;T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	.;.;.;M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N;.;.;.;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.087	T;.;.;.;D;T;T
Sift4G	Benign	0.19	T;T;T;T;T;T;T
Polyphen		1.0	D;.;D;P;D;D;P
Vest4		0.55
MVP		0.26
MPC		0.37
ClinPred		0.034	T
GERP RS		5.9
Varity_R		0.29
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41274050; hg19: chr10-52573772;