10-4990092-C-T

Position:

• chr10-4990092-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.930-54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,607,422 control chromosomes in the GnomAD database, including 39,058 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3163 hom., cov: 31)
  • Exomes 𝑓: 0.21 (35895 hom.)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.806

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=-0.93).
• BP6: Variant 10-4990092-C-T is Benign according to our data. Variant chr10-4990092-C-T is described in ClinVar as [Benign]. Clinvar id is 1293763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C2	NM_001393392.1	c.930-54G>A		intron_variant		ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C2	ENST00000380753.9	c.930-54G>A		intron_variant		1	NM_001393392.1	ENSP00000370129	P1
AKR1C2	ENST00000421196.7	c.852-54G>A		intron_variant		1		ENSP00000392694
AKR1C2	ENST00000460124.5	n.2390-54G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28822 AN: 151954 Hom.: 3162 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0830

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.211 AC: 306352 AN: 1455350 Hom.: 35895 AF XY: 0.206 AC XY: 149285 AN XY: 724160

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.0902

Gnomad4 EAS exome AF: 0.000455

Gnomad4 SAS exome AF: 0.0961

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.190 AC: 28835 AN: 152072 Hom.: 3163 Cov.: 31 AF XY: 0.191 AC XY: 14167 AN XY: 74336

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0830

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0859

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.148

Alfa AF: 0.159 Hom.: 481

Bravo AF: 0.173

Asia WGS AF: 0.0480 AC: 167 AN: 3478

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	-0.93
CADD	Benign	1.2
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs12774733; hg19: chr10-5032284;