Variant 10-4990047-A-AG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001393392.1(AKR1C2):c.930-10_930-9insC variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,596,778 control chromosomes in the GnomAD database, including 42,250 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3947 hom., cov: 25)

Exomes 𝑓: 0.22 ( 38303 hom. )

Consequence

AKR1C2
NM_001393392.1 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.670

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 10-4990047-A-AG is Benign according to our data. Variant chr10-4990047-A-AG is described in ClinVar as [Benign]. Clinvar id is 1229377.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 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.930-10_930-9insC		splice_polypyrimidine_tract_variant, intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9 linkuse as main transcript	c.930-10_930-9insC	splice_polypyrimidine_tract_variant, intron_variant	1	NM_001393392.1	P1	P52895-1
AKR1C2	ENST00000421196.7 linkuse as main transcript	c.852-10_852-9insC	splice_polypyrimidine_tract_variant, intron_variant	1
AKR1C2	ENST00000460124.5 linkuse as main transcript	n.2390-10_2390-9insC	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30840

AN:

151550

Hom.:

3944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.594

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.265

AC:

63791

AN:

240702

Hom.:

10300

AF XY:

0.266

AC XY:

34755

AN XY:

130724

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.582

Gnomad SAS exome

AF:

0.369

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.217

AC:

312989

AN:

1445112

Hom.:

38303

Cov.:

AF XY:

0.221

AC XY:

159153

AN XY:

718888

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.388

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.586

Gnomad4 SAS exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.222

GnomAD4 genome

AF:

0.203

AC:

30859

AN:

151666

Hom.:

3947

Cov.:

AF XY:

0.214

AC XY:

15821

AN XY:

74072

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.595

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.226

Alfa

AF:

0.109

Hom.:

279

Asia WGS

AF:

0.413

AC:

1431

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 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.28

Position offset: -9

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