rs41274050

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.65

Publications

13 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 779433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 57 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
A1CF	NM_014576.4	MANE Select	c.1168G>A	p.Gly390Ser	missense	Exon 10 of 13	NP_055391.2
A1CF	NM_001198819.2		c.1216G>A	p.Gly406Ser	missense	Exon 12 of 15	NP_001185748.1	F8W9F8
A1CF	NM_001198820.2		c.1192G>A	p.Gly398Ser	missense	Exon 11 of 14	NP_001185749.1	Q9NQ94-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
A1CF	ENST00000373997.8	TSL:1 MANE Select	c.1168G>A	p.Gly390Ser	missense	Exon 10 of 13	ENSP00000363109.3	Q9NQ94-2
A1CF	ENST00000373993.6	TSL:1	c.1192G>A	p.Gly398Ser	missense	Exon 9 of 12	ENSP00000363105.1	Q9NQ94-1
A1CF	ENST00000855032.1		c.1246G>A	p.Gly416Ser	missense	Exon 12 of 15	ENSP00000525091.1

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

894

AN:

152074

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00525

AC:

1317

AN:

250812

AF XY:

0.00516

show subpopulations

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 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.:

Cov.:

AF XY:

0.00772

AC XY:

5612

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33450

American (AMR)

AF:

0.00573

AC:

256

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00287

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39680

South Asian (SAS)

AF:

0.000406

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00152

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00175

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00961

AC:

10682

AN:

1111788

Other (OTH)

AF:

0.00676

AC:

408

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

614

1228

1843

2457

3071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00587

AC:

894

AN:

152192

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

41524

American (AMR)

AF:

0.00896

AC:

137

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00925

AC:

629

AN:

68006

Other (OTH)

AF:

0.00902

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00762

Hom.:

Bravo

AF:

0.00634

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00826

AC:

ExAC

AF:

0.00532

AC:

646

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00911

EpiControl

AF:

0.00872

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

M_CAP

Benign

0.0059

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

PhyloP100

5.6

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

REVEL

Benign

0.18

Sift

Benign

0.087

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.55

MVP

0.26

MPC

0.37

ClinPred

0.034

GERP RS

5.9

Varity_R

0.29

gMVP

0.91

Mutation Taster

=21/79

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over