Variant 10-50816265-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_014576.4(A1CF):c.882C>T(p.Ser294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,613,282 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 26 hom. )

Consequence

A1CF
NM_014576.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0300

Variant links:

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]

A1CF links:

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]

ASAH2B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 10-50816265-G-A is Benign according to our data. Variant chr10-50816265-G-A is described in ClinVar as [Benign]. Clinvar id is 774682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.03 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A1CF	NM_014576.4 linkuse as main transcript	c.882C>T	p.Ser294=	synonymous_variant	9/13	ENST00000373997.8	NP_055391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A1CF	ENST00000373997.8 linkuse as main transcript	c.882C>T	p.Ser294=	synonymous_variant	9/13	1	NM_014576.4	ENSP00000363109	A1	Q9NQ94-2

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

431

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00241

AC:

601

AN:

249662

Hom.:

AF XY:

0.00240

AC XY:

324

AN XY:

134962

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00260

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.00437

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00466

AC:

6809

AN:

1461108

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

3349

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.000957

Gnomad4 AMR exome

AF:

0.000381

Gnomad4 ASJ exome

AF:

0.00257

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00581

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00283

AC:

431

AN:

152174

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.000917

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00497

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00398

Hom.:

Bravo

AF:

0.00263

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00404

EpiControl

AF:

0.00374

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over