10-4992025-C-T

Position:

• chr10-4992025-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001393392.1(AKR1C2):​c.847-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 51,062 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (204 hom., cov: 18)
  • Exomes 𝑓: 0.071 (128 hom.)
  • Failed GnomAD Quality Control
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.913

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 10-4992025-C-T is Benign according to our data. Variant chr10-4992025-C-T is described in ClinVar as [Benign]. Clinvar id is 1231590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1	c.847-112G>A		intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9	c.847-112G>A		intron_variant		1	NM_001393392.1	P1
AKR1C2	ENST00000421196.7	c.769-112G>A		intron_variant		1
AKR1C2	ENST00000460124.5	n.2307-112G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 7963 AN: 132006 Hom.: 204 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000207

Gnomad SAS AF: 0.00962

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.0302

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.0638

GnomAD4 exome AF: 0.0709 AC: 3619 AN: 51062 Hom.: 128 AF XY: 0.0651 AC XY: 1731 AN XY: 26592

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.0473

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.0876

Gnomad4 NFE exome AF: 0.0953

Gnomad4 OTH exome AF: 0.0733

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0603 AC: 7962 AN: 132116 Hom.: 204 Cov.: 18 AF XY: 0.0583 AC XY: 3675 AN XY: 63056

Gnomad4 AFR AF: 0.0214

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.000208

Gnomad4 SAS AF: 0.00964

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.0895

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0241 Hom.: 9

Bravo AF: 0.0582

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.97
CADD	Benign	3.5
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs113280686; hg19: chr10-5034217;