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GeneBe

rs17306779

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001818.5(AKR1C4):ā€‹c.105A>Gā€‹(p.Val35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,736 control chromosomes in the GnomAD database, including 39,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.19 ( 2875 hom., cov: 32)
Exomes š‘“: 0.22 ( 36440 hom. )

Consequence

AKR1C4
NM_001818.5 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -1.62
Variant links:
Genes affected
AKR1C4 (HGNC:387): (aldo-keto reductase family 1 member C4) 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 bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver. 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 -21 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=-0.93).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-5200201-A-G is Benign according to our data. Variant chr10-5200201-A-G is described in ClinVar as [Benign]. Clinvar id is 1229360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=-1.62 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 = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AKR1C4NM_001818.5 linkuse as main transcriptc.105A>G p.Val35= synonymous_variant 2/9 ENST00000263126.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AKR1C4ENST00000263126.3 linkuse as main transcriptc.105A>G p.Val35= synonymous_variant 2/91 NM_001818.5 P1
AKR1C4ENST00000380448.5 linkuse as main transcriptc.105A>G p.Val35= synonymous_variant 4/115 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.187
AC:
28388
AN:
152188
Hom.:
2874
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.113
Gnomad AMI
AF:
0.167
Gnomad AMR
AF:
0.226
Gnomad ASJ
AF:
0.192
Gnomad EAS
AF:
0.136
Gnomad SAS
AF:
0.163
Gnomad FIN
AF:
0.190
Gnomad MID
AF:
0.218
Gnomad NFE
AF:
0.227
Gnomad OTH
AF:
0.187
GnomAD3 exomes
AF:
0.205
AC:
51326
AN:
250916
Hom.:
5552
AF XY:
0.205
AC XY:
27749
AN XY:
135606
show subpopulations
Gnomad AFR exome
AF:
0.112
Gnomad AMR exome
AF:
0.240
Gnomad ASJ exome
AF:
0.188
Gnomad EAS exome
AF:
0.141
Gnomad SAS exome
AF:
0.166
Gnomad FIN exome
AF:
0.187
Gnomad NFE exome
AF:
0.232
Gnomad OTH exome
AF:
0.214
GnomAD4 exome
AF:
0.220
AC:
320870
AN:
1461430
Hom.:
36440
Cov.:
32
AF XY:
0.217
AC XY:
157978
AN XY:
726990
show subpopulations
Gnomad4 AFR exome
AF:
0.111
Gnomad4 AMR exome
AF:
0.244
Gnomad4 ASJ exome
AF:
0.186
Gnomad4 EAS exome
AF:
0.101
Gnomad4 SAS exome
AF:
0.164
Gnomad4 FIN exome
AF:
0.199
Gnomad4 NFE exome
AF:
0.233
Gnomad4 OTH exome
AF:
0.209
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.186
AC:
28402
AN:
152306
Hom.:
2875
Cov.:
32
AF XY:
0.185
AC XY:
13791
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.113
Gnomad4 AMR
AF:
0.227
Gnomad4 ASJ
AF:
0.192
Gnomad4 EAS
AF:
0.136
Gnomad4 SAS
AF:
0.163
Gnomad4 FIN
AF:
0.190
Gnomad4 NFE
AF:
0.227
Gnomad4 OTH
AF:
0.184
Alfa
AF:
0.215
Hom.:
2487
Bravo
AF:
0.187
Asia WGS
AF:
0.144
AC:
503
AN:
3478
EpiCase
AF:
0.221
EpiControl
AF:
0.224

ClinVar

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 27, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxOct 15, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.31
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: rs17306779; hg19: chr10-5242164; COSMIC: COSV54122750; COSMIC: COSV54122750; API