dbSNP rs10994860: A1CF:c.-270G>A (chr10-50885664-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000395489.7(A1CF):c.-389G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.184 in 152,084 control chromosomes in the GnomAD database, including 2,735 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 0.18 ( 2735 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

A1CF
ENST00000395489.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.92

Publications

32 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395489.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
A1CF	NM_014576.4	MANE Select	c.-177G>A	upstream_gene	N/A	NP_055391.2
A1CF	NM_001198819.2		c.-389G>A	upstream_gene	N/A	NP_001185748.1	F8W9F8
A1CF	NM_001198820.2		c.-296G>A	upstream_gene	N/A	NP_001185749.1	Q9NQ94-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
A1CF	ENST00000855032.1		c.-270G>A	5_prime_UTR	Exon 1 of 15	ENSP00000525091.1
A1CF	ENST00000395489.7	TSL:2	c.-389G>A	5_prime_UTR	Exon 1 of 15	ENSP00000378868.3	F8W9F8
A1CF	ENST00000373995.7	TSL:2	c.-248G>A	5_prime_UTR	Exon 1 of 13	ENSP00000363107.3	Q9NQ94-4

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27981

AN:

151966

Hom.:

2728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.0456

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.175

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.184

AC:

28008

AN:

152084

Hom.:

2735

Cov.:

AF XY:

0.187

AC XY:

13885

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.209

AC:

8690

AN:

41512

American (AMR)

AF:

0.128

AC:

1955

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

690

AN:

3464

East Asian (EAS)

AF:

0.0459

AC:

238

AN:

5182

South Asian (SAS)

AF:

0.213

AC:

1029

AN:

4826

European-Finnish (FIN)

AF:

0.279

AC:

2941

AN:

10536

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11887

AN:

67980

Other (OTH)

AF:

0.181

AC:

382

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1148

2296

3445

4593

5741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.174

Hom.:

3057

Bravo

AF:

0.173

Asia WGS

AF:

0.165

AC:

573

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

5.9

PromoterAI

-0.12

Neutral

(source)

Mutation Taster

=293/7

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over