Variant 10-4990092-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001393392.1(AKR1C2):c.930-54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,607,422 control chromosomes in the GnomAD database, including 39,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 3163 hom., cov: 31)

Exomes 𝑓: 0.21 ( 35895 hom. )

Consequence

AKR1C2
NM_001393392.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.806

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]

AKR1C2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 10-4990092-C-T is Benign according to our data. Variant chr10-4990092-C-T is described in ClinVar as [Benign]. Clinvar id is 1293763.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1 linkuse as main transcript	c.930-54G>A		intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9 linkuse as main transcript	c.930-54G>A	intron_variant	1	NM_001393392.1	P1	P52895-1
AKR1C2	ENST00000421196.7 linkuse as main transcript	c.852-54G>A	intron_variant	1
AKR1C2	ENST00000460124.5 linkuse as main transcript	n.2390-54G>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28822

AN:

151954

Hom.:

3162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.0830

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.0850

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.150

GnomAD4 exome

AF:

0.211

AC:

306352

AN:

1455350

Hom.:

35895

AF XY:

0.206

AC XY:

149285

AN XY:

724160

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.0902

Gnomad4 EAS exome

AF:

0.000455

Gnomad4 SAS exome

AF:

0.0961

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.190

AC:

28835

AN:

152072

Hom.:

3163

Cov.:

AF XY:

0.191

AC XY:

14167

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.0830

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.0859

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.159

Hom.:

481

Bravo

AF:

0.173

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

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 submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.2

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over