Variant 10-4995523-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001393392.1(AKR1C2):c.681-39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 3 hom., cov: 20)

Exomes 𝑓: 0.14 ( 11806 hom. )

Failed GnomAD Quality Control

Consequence

AKR1C2
NM_001393392.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.768

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 10-4995523-G-C is Benign according to our data. Variant chr10-4995523-G-C is described in ClinVar as [Benign]. Clinvar id is 1237642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0516 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.681-39C>G		intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9 linkuse as main transcript	c.681-39C>G	intron_variant		1	NM_001393392.1	P1	P52895-1
AKR1C2	ENST00000421196.7 linkuse as main transcript	c.603-39C>G	intron_variant		1
	ENST00000451575.6 linkuse as main transcript	n.36G>C	non_coding_transcript_exon_variant	1/3	3
AKR1C2	ENST00000460124.5 linkuse as main transcript	n.2141-39C>G	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1279

AN:

119642

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00583

Gnomad AMI

AF:

0.00127

Gnomad AMR

AF:

0.0180

Gnomad ASJ

AF:

0.0215

Gnomad EAS

AF:

0.0605

Gnomad SAS

AF:

0.0362

Gnomad FIN

AF:

0.00808

Gnomad MID

AF:

0.0200

Gnomad NFE

AF:

0.00943

Gnomad OTH

AF:

0.0133

GnomAD3 exomes

AF:

0.234

AC:

51774

AN:

220930

Hom.:

5181

AF XY:

0.238

AC XY:

28567

AN XY:

120026

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.361

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.520

Gnomad SAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.140

AC:

172038

AN:

1225998

Hom.:

11806

Cov.:

AF XY:

0.143

AC XY:

87330

AN XY:

609048

show subpopulations

Gnomad4 AFR exome

AF:

0.0758

Gnomad4 AMR exome

AF:

0.308

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.398

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.0672

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.0107

AC:

1280

AN:

119744

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

693

AN XY:

57504

show subpopulations

Gnomad4 AFR

AF:

0.00584

Gnomad4 AMR

AF:

0.0179

Gnomad4 ASJ

AF:

0.0215

Gnomad4 EAS

AF:

0.0604

Gnomad4 SAS

AF:

0.0362

Gnomad4 FIN

AF:

0.00808

Gnomad4 NFE

AF:

0.00943

Gnomad4 OTH

AF:

0.0145

Alfa

AF:

0.0929

Hom.:

101

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.94

CADD

Benign

0.66

DANN

Benign

0.69

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.

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