Variant chr10-4991824-T-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.929+7A>G 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. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 2639 hom., cov: 12)

Exomes 𝑓: 0.28 ( 14526 hom. )

Consequence

AKR1C2
NM_001393392.1 splice_region, intron

Scores

Splicing: ADA: 0.00001381

Clinical Significance

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

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]

AKR1C2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 10-4991824-T-C is Benign according to our data. Variant chr10-4991824-T-C is described in ClinVar as [Benign]. Clinvar id is 1224027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-4991824-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 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.929+7A>G		splice_region_variant, intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9 linkuse as main transcript	c.929+7A>G	splice_region_variant, intron_variant	1	NM_001393392.1	P1	P52895-1
AKR1C2	ENST00000421196.7 linkuse as main transcript	c.851+7A>G	splice_region_variant, intron_variant	1
AKR1C2	ENST00000460124.5 linkuse as main transcript	n.2389+7A>G	splice_region_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

21123

AN:

89290

Hom.:

2638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.295

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.268

GnomAD3 exomes

AF:

0.296

AC:

14564

AN:

49132

Hom.:

2738

AF XY:

0.302

AC XY:

7646

AN XY:

25280

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.366

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.600

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.199

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.276

AC:

98685

AN:

357042

Hom.:

14526

Cov.:

AF XY:

0.285

AC XY:

53776

AN XY:

188566

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.594

Gnomad4 SAS exome

AF:

0.410

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.237

AC:

21136

AN:

89368

Hom.:

2639

Cov.:

AF XY:

0.244

AC XY:

9971

AN XY:

40928

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.344

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.600

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.236

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.271

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

-0.95

CADD

Benign

0.50

DANN

Benign

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0020

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