10-4991964-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001393392.1(AKR1C2):c.847-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (107 hom., cov: 15)
  • Exomes 𝑓: 0.0032 (23 hom.)
  • Failed GnomAD Quality Control
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0980

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-4991964-A-G is Benign according to our data. Variant chr10-4991964-A-G is described in ClinVar as [Benign]. Clinvar id is 1241271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1	c.847-51T>C		intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9	c.847-51T>C		intron_variant		1	NM_001393392.1	P1
AKR1C2	ENST00000421196.7	c.769-51T>C		intron_variant		1
AKR1C2	ENST00000460124.5	n.2307-51T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2544 AN: 122764 Hom.: 106 Cov.: 15 FAILED QC

Gnomad AFR AF: 0.0751

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000616

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000390

Gnomad OTH AF: 0.0235

GnomAD3 exomes AF: 0.00989 AC: 453 AN: 45786 Hom.: 12 AF XY: 0.00824 AC XY: 195 AN XY: 23662

Gnomad AFR exome AF: 0.0819

Gnomad AMR exome AF: 0.00609

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000686

Gnomad OTH exome AF: 0.00644

GnomAD4 exome AF: 0.00322 AC: 828 AN: 257042 Hom.: 23 Cov.: 0 AF XY: 0.00265 AC XY: 361 AN XY: 135972

Gnomad4 AFR exome AF: 0.0766

Gnomad4 AMR exome AF: 0.00613

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.00578

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0208 AC: 2553 AN: 122868 Hom.: 107 Cov.: 15 AF XY: 0.0206 AC XY: 1192 AN XY: 57838

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000617

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000390

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0198 Hom.: 8

Bravo AF: 0.0266

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.52
Dann	Benign	0.50

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: rs559779441; hg19: chr10-5034156;