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GeneBe

10-4966996-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001353.6(AKR1C1):c.322T>C(p.Leu108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,613,908 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 9 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 15 hom. )

Consequence

AKR1C1
NM_001353.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.690
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=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-4966996-T-C is Benign according to our data. Variant chr10-4966996-T-C is described in ClinVar as [Benign]. Clinvar id is 784081.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=-0.69 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 = 0.00572 (871/152332) while in subpopulation AFR AF= 0.0169 (702/41568). AF 95% confidence interval is 0.0159. There are 9 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. Median coverage is 33. 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 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKR1C1NM_001353.6 linkuse as main transcriptc.322T>C p.Leu108= synonymous_variant 3/9 ENST00000380872.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKR1C1ENST00000380872.9 linkuse as main transcriptc.322T>C p.Leu108= synonymous_variant 3/91 NM_001353.6 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00572
AC:
870
AN:
152214
Hom.:
9
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00119
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00275
AC:
690
AN:
251080
Hom.:
7
AF XY:
0.00235
AC XY:
319
AN XY:
135690
show subpopulations
Gnomad AFR exome
AF:
0.0190
Gnomad AMR exome
AF:
0.00341
Gnomad ASJ exome
AF:
0.00685
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00134
Gnomad NFE exome
AF:
0.00130
Gnomad OTH exome
AF:
0.00294
GnomAD4 exome
AF:
0.00139
AC:
2035
AN:
1461576
Hom.:
15
Cov.:
30
AF XY:
0.00133
AC XY:
969
AN XY:
727078
show subpopulations
Gnomad4 AFR exome
AF:
0.0206
Gnomad4 AMR exome
AF:
0.00356
Gnomad4 ASJ exome
AF:
0.00620
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00109
Gnomad4 NFE exome
AF:
0.000703
Gnomad4 OTH exome
AF:
0.00247
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00572
AC:
871
AN:
152332
Hom.:
9
Cov.:
33
AF XY:
0.00558
AC XY:
416
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0169
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00634
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.00119
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00181
Hom.:
0
Bravo
AF:
0.00629
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00164
EpiControl
AF:
0.00184

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
0.59
Dann
Benign
0.55

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: rs140966911; hg19: chr10-5009188; COSMIC: COSV101080620; COSMIC: COSV101080620; API