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GeneBe

rs1138600

chr10-4968380-A-Gchr10-4968380-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001353.6(AKR1C1):c.441A>G(p.Thr147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 148,896 control chromosomes in the GnomAD database, including 73,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.99 ( 73694 hom., cov: 24)
Exomes 𝑓: 1.0 ( 693643 hom. )
Failed GnomAD Quality Control

Consequence

AKR1C1
NM_001353.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -10.2
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 -15 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=-1.03).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-4968380-A-G is Benign according to our data. Variant chr10-4968380-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 768347.Status of the report is criteria_provided_single_submitter, 1 stars.
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=-10.2 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKR1C1NM_001353.6 linkuse as main transcriptc.441A>G p.Thr147= synonymous_variant 4/9 ENST00000380872.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKR1C1ENST00000380872.9 linkuse as main transcriptc.441A>G p.Thr147= synonymous_variant 4/91 NM_001353.6 P1
AKR1C1ENST00000442997.5 linkuse as main transcriptc.342A>G p.Thr114= synonymous_variant 4/73
AKR1C1ENST00000380859.1 linkuse as main transcriptc.447A>G p.Thr149= synonymous_variant 4/63
AKR1C1ENST00000477661.1 linkuse as main transcriptn.1898A>G non_coding_transcript_exon_variant 3/85

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.995
AC:
148022
AN:
148782
Hom.:
73634
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.991
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.995
Gnomad ASJ
AF:
0.989
Gnomad EAS
AF:
0.992
Gnomad SAS
AF:
0.996
Gnomad FIN
AF:
0.998
Gnomad MID
AF:
0.997
Gnomad NFE
AF:
0.997
Gnomad OTH
AF:
0.994
GnomAD3 exomes
AF:
0.997
AC:
179348
AN:
179892
Hom.:
89404
AF XY:
0.997
AC XY:
95085
AN XY:
95372
show subpopulations
Gnomad AFR exome
AF:
0.990
Gnomad AMR exome
AF:
0.998
Gnomad ASJ exome
AF:
0.994
Gnomad EAS exome
AF:
0.997
Gnomad SAS exome
AF:
0.996
Gnomad FIN exome
AF:
0.998
Gnomad NFE exome
AF:
0.998
Gnomad OTH exome
AF:
0.997
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.997
AC:
1391089
AN:
1394908
Hom.:
693643
Cov.:
27
AF XY:
0.997
AC XY:
690404
AN XY:
692326
show subpopulations
Gnomad4 AFR exome
AF:
0.990
Gnomad4 AMR exome
AF:
0.999
Gnomad4 ASJ exome
AF:
0.992
Gnomad4 EAS exome
AF:
0.996
Gnomad4 SAS exome
AF:
0.996
Gnomad4 FIN exome
AF:
0.998
Gnomad4 NFE exome
AF:
0.998
Gnomad4 OTH exome
AF:
0.997
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.995
AC:
148139
AN:
148896
Hom.:
73694
Cov.:
24
AF XY:
0.995
AC XY:
72332
AN XY:
72716
show subpopulations
Gnomad4 AFR
AF:
0.991
Gnomad4 AMR
AF:
0.995
Gnomad4 ASJ
AF:
0.989
Gnomad4 EAS
AF:
0.992
Gnomad4 SAS
AF:
0.997
Gnomad4 FIN
AF:
0.998
Gnomad4 NFE
AF:
0.997
Gnomad4 OTH
AF:
0.994
Alfa
AF:
0.994
Hom.:
12477
Bravo
AF:
0.996

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
Cadd
Benign
3.8
Dann
Benign
0.18
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs1138600; hg19: chr10-5010572; COSMIC: COSV66498428; COSMIC: COSV66498428; API