rs200698968

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001393392.1(AKR1C2):​c.929+7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 12)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AKR1C2
NM_001393392.1 splice_region, intron

Scores

2
Splicing: ADA: 0.0001058
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AKR1C2NM_001393392.1 linkc.929+7A>T splice_region_variant, intron_variant Intron 8 of 8 ENST00000380753.9 NP_001380321.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AKR1C2ENST00000380753.9 linkc.929+7A>T splice_region_variant, intron_variant Intron 8 of 8 1 NM_001393392.1 ENSP00000370129.4 P52895-1
AKR1C2ENST00000421196.7 linkc.851+7A>T splice_region_variant, intron_variant Intron 7 of 7 1 ENSP00000392694.2 B4DK69
AKR1C2ENST00000460124.5 linkn.2389+7A>T splice_region_variant, intron_variant Intron 7 of 7 5

Frequencies

GnomAD3 genomes
Cov.:
12
GnomAD4 exome
AF:
0.00000272
AC:
1
AN:
367136
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
193740
show subpopulations
Gnomad4 AFR exome
AF:
0.0000986
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.46
DANN
Benign
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00011
dbscSNV1_RF
Benign
0.0020
SpliceAI score (max)
0.040
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: rs200698968; hg19: chr10-5034016; API