rs2854466

Positions:

• chr10-4997372-G-A
• chr10-4997372-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393392.1(AKR1C2):​c.570+1253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,284 control chromosomes in the GnomAD database, including 4,024 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (4018 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6 hom.)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1	c.570+1253C>T		intron_variant		ENST00000380753.9
LOC101928051	XR_001747340.2	n.471G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9	c.570+1253C>T		intron_variant		1	NM_001393392.1	P1
	ENST00000451575.6	n.423G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31040 AN: 151904 Hom.: 4013 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.173 AC: 45 AN: 260 Hom.: 6 Cov.: 0 AF XY: 0.158 AC XY: 24 AN XY: 152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.204 AC: 31063 AN: 152024 Hom.: 4018 Cov.: 32 AF XY: 0.215 AC XY: 15969 AN XY: 74288

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.225

Alfa AF: 0.200 Hom.: 863

Bravo AF: 0.208

Asia WGS AF: 0.418 AC: 1449 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.64

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: rs2854466; hg19: chr10-5039564;