rs11474

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000380753.9(AKR1C2):​c.515T>A​(p.Leu172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

AKR1C2
ENST00000380753.9 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66
Variant links:
Genes affected
AKR1C2 (HGNC:385): (aldo-keto reductase family 1 member C2) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme binds bile acid with high affinity, and shows minimal 3-alpha-hydroxysteroid dehydrogenase activity. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.029745638).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AKR1C2NM_001393392.1 linkuse as main transcriptc.515T>A p.Leu172Gln missense_variant 5/9 ENST00000380753.9 NP_001380321.1
LOC101928051XR_001747340.2 linkuse as main transcriptn.1779A>T non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AKR1C2ENST00000380753.9 linkuse as main transcriptc.515T>A p.Leu172Gln missense_variant 5/91 NM_001393392.1 ENSP00000370129 P1P52895-1
AKR1C2ENST00000421196.7 linkuse as main transcriptc.437T>A p.Leu146Gln missense_variant 4/81 ENSP00000392694
AKR1C2ENST00000604507.5 linkuse as main transcriptc.515T>A p.Leu172Gln missense_variant 6/75 ENSP00000474566
AKR1C2ENST00000460124.5 linkuse as main transcriptn.1975T>A non_coding_transcript_exon_variant 4/85

Frequencies

GnomAD3 genomes
AF:
0.000256
AC:
39
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000119
AC:
30
AN:
251446
Hom.:
0
AF XY:
0.000140
AC XY:
19
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000326
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000149
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000283
AC:
413
AN:
1461814
Hom.:
0
Cov.:
31
AF XY:
0.000286
AC XY:
208
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.000346
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000256
AC:
39
AN:
152302
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000150
Hom.:
0
Bravo
AF:
0.000223
ExAC
AF:
0.000157
AC:
19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
4.2
DANN
Benign
0.83
DEOGEN2
Benign
0.029
T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.69
T;T;T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.030
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-1.7
N;.;.
MutationTaster
Benign
0.96
N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
5.7
N;N;.
REVEL
Benign
0.042
Sift
Benign
1.0
T;T;.
Sift4G
Benign
1.0
T;T;.
Polyphen
0.0
B;B;.
Vest4
0.32
MVP
0.11
MPC
0.12
ClinPred
0.0023
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.26

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: rs11474; hg19: chr10-5040872; COSMIC: COSV99068850; COSMIC: COSV99068850; API