chr1-19308211-C-T

Variant summary

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

The NM_003689.4(AKR7A2):​c.538G>A​(p.Glu180Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,614,086 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.012 ( 41 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 23 hom. )

Consequence

AKR7A2
NM_003689.4 missense

Scores

1
4
13

Clinical Significance

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

Conservation

PhyloP100: 7.26
Variant links:
Genes affected
AKR7A2 (HGNC:389): (aldo-keto reductase family 7 member A2) The protein encoded by this gene belongs to the aldo/keto reductase (AKR) superfamily and AKR7 family, which are involved in the detoxification of aldehydes and ketones. The AKR7 family consists of 3 genes that are present in a cluster on the p arm of chromosome 1. This protein, thought to be localized in the golgi, catalyzes the NADPH-dependent reduction of succinic semialdehyde to the endogenous neuromodulator, gamma-hydroxybutyrate. It may also function as a detoxication enzyme in the reduction of aflatoxin B1 and 2-carboxybenzaldehyde. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

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=0.008173585).
BP6
Variant 1-19308211-C-T is Benign according to our data. Variant chr1-19308211-C-T is described in ClinVar as [Benign]. Clinvar id is 788501.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 = 0.0117 (1785/152260) while in subpopulation AFR AF= 0.0415 (1725/41540). AF 95% confidence interval is 0.0399. There are 41 homozygotes in gnomad4. There are 783 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AKR7A2NM_003689.4 linkc.538G>A p.Glu180Lys missense_variant Exon 3 of 7 ENST00000235835.8 NP_003680.2 O43488V9HWA2
AKR7A2XM_047433095.1 linkc.538G>A p.Glu180Lys missense_variant Exon 3 of 4 XP_047289051.1
AKR7A2NM_001320979.1 linkc.486+244G>A intron_variant Intron 2 of 5 NP_001307908.1 B4DZX4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AKR7A2ENST00000235835.8 linkc.538G>A p.Glu180Lys missense_variant Exon 3 of 7 1 NM_003689.4 ENSP00000235835.3 O43488

Frequencies

GnomAD3 genomes
AF:
0.0117
AC:
1781
AN:
152142
Hom.:
41
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0416
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00862
GnomAD3 exomes
AF:
0.00305
AC:
766
AN:
251462
Hom.:
19
AF XY:
0.00205
AC XY:
279
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.0423
Gnomad AMR exome
AF:
0.00185
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00111
AC:
1626
AN:
1461826
Hom.:
23
Cov.:
31
AF XY:
0.000942
AC XY:
685
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.0398
Gnomad4 AMR exome
AF:
0.00208
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.00235
GnomAD4 genome
AF:
0.0117
AC:
1785
AN:
152260
Hom.:
41
Cov.:
33
AF XY:
0.0105
AC XY:
783
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0415
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00853
Alfa
AF:
0.00581
Hom.:
15
Bravo
AF:
0.0136
ESP6500AA
AF:
0.0404
AC:
178
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00382
AC:
464
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Apr 26, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.039
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.26
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D
MetaRNN
Benign
0.0082
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.77
N
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.19
Sift
Benign
0.095
T
Sift4G
Benign
0.18
T
Polyphen
0.50
P
Vest4
0.78
MVP
0.43
MPC
0.14
ClinPred
0.10
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.58
gMVP
0.31

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.

Other links and lift over

dbSNP: rs859210; hg19: chr1-19634705; API