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rs7097713

chr10-4968923-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_001353.6(AKR1C1):c.549G>A(p.Lys183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,614,164 control chromosomes in the GnomAD database, including 49 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 0.010 ( 31 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 18 hom. )

Consequence

AKR1C1
NM_001353.6 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.516
Variant links:
Genes affected
AKR1C1 (HGNC:384): (aldo-keto reductase family 1 member C1) 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 by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.516 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00999 (1521/152276) while in subpopulation AFR AF= 0.0348 (1445/41566). AF 95% confidence interval is 0.0333. There are 31 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKR1C1NM_001353.6 linkuse as main transcriptc.549G>A p.Lys183= synonymous_variant 5/9 ENST00000380872.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKR1C1ENST00000380872.9 linkuse as main transcriptc.549G>A p.Lys183= synonymous_variant 5/91 NM_001353.6 P1
AKR1C1ENST00000442997.5 linkuse as main transcriptc.450G>A p.Lys150= synonymous_variant 5/73
AKR1C1ENST00000380859.1 linkuse as main transcriptc.555G>A p.Lys185= synonymous_variant 5/63
AKR1C1ENST00000477661.1 linkuse as main transcriptn.2006G>A non_coding_transcript_exon_variant 4/85

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0100
AC:
1521
AN:
152158
Hom.:
31
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0349
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00360
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:
0.0000735
Gnomad OTH
AF:
0.00766
GnomAD3 exomes
AF:
0.00256
AC:
645
AN:
251476
Hom.:
14
AF XY:
0.00184
AC XY:
250
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.0355
Gnomad AMR exome
AF:
0.00156
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00102
AC:
1496
AN:
1461888
Hom.:
18
Cov.:
32
AF XY:
0.000884
AC XY:
643
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0372
Gnomad4 AMR exome
AF:
0.00168
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:
0.0000144
Gnomad4 OTH exome
AF:
0.00220
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00999
AC:
1521
AN:
152276
Hom.:
31
Cov.:
32
AF XY:
0.00953
AC XY:
710
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0348
Gnomad4 AMR
AF:
0.00360
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00758
Alfa
AF:
0.00252
Hom.:
4
Bravo
AF:
0.0117
Asia WGS
AF:
0.00318
AC:
12
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
5.1
Dann
Benign
0.45

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: rs7097713; hg19: chr10-5011115; API