Variant 13-76957357-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001258406.2(ACOD1):c.818G>A(p.Arg273His) variant causes a missense change. The variant allele was found at a frequency of 0.00135 in 1,550,608 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 7 hom. )

Consequence

ACOD1
NM_001258406.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.62

Variant links:

Genes affected

ACOD1 (HGNC:33904): (aconitate decarboxylase 1) Enables aconitate decarboxylase activity. Involved in defense response; positive regulation of antimicrobial humoral response; and tolerance induction to lipopolysaccharide. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACOD1 links:

LOC105370269 (HGNC:):

LOC105370269 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008932799).

BP6

Variant 13-76957357-G-A is Benign according to our data. Variant chr13-76957357-G-A is described in ClinVar as [Benign]. Clinvar id is 784272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00688 (1048/152322) while in subpopulation AFR AF= 0.0229 (954/41570). AF 95% confidence interval is 0.0217. There are 15 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ACOD1	NM_001258406.2 linkuse as main transcript	c.818G>A	p.Arg273His	missense_variant	5/5	ENST00000377462.6	NP_001245335.1
LOC105370269	XR_001749929.1 linkuse as main transcript	n.213-14486C>T		intron_variant, non_coding_transcript_variant
ACOD1	XM_047430581.1 linkuse as main transcript	c.722G>A	p.Arg241His	missense_variant	4/4		XP_047286537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOD1	ENST00000377462.6 linkuse as main transcript	c.818G>A	p.Arg273His	missense_variant	5/5	5	NM_001258406.2	ENSP00000366682	P1

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1047

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00123

AC:

183

AN:

148998

Hom.:

AF XY:

0.000922

AC XY:

AN XY:

80236

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.000956

Gnomad EAS exome

AF:

0.0000928

Gnomad SAS exome

AF:

0.0000444

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000219

Gnomad OTH exome

AF:

0.000696

GnomAD4 exome

AF:

0.000748

AC:

1046

AN:

1398286

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

455

AN XY:

689660

show subpopulations

Gnomad4 AFR exome

AF:

0.0207

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00167

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000883

Gnomad4 FIN exome

AF:

0.0000623

Gnomad4 NFE exome

AF:

0.000178

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00688

AC:

1048

AN:

152322

Hom.:

Cov.:

AF XY:

0.00660

AC XY:

492

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0229

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00321

Hom.:

Bravo

AF:

0.00745

ExAC

AF:

0.00112

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

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	Jul 10, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0089

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

0.53

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.20

Sift

Benign

0.14

T;T

Sift4G

Uncertain

0.013

D;D

Vest4

0.12

MVP

0.061

ClinPred

0.050

GERP RS

4.0

Varity_R

0.099

gMVP

0.71

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