rs9804392

Variant names:

• chr10-4994249-G-A
• rs9804392
• NM_001393392.1:c.846+1070C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-4994249-G-A
• chr10-4994249-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393392.1(AKR1C2):​c.846+1070C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 127,842 control chromosomes in the GnomAD database, including 1,998 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 0.18 (1998 hom., cov: 33)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to testicular 17,20-desmolase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C2	NM_001393392.1	c.846+1070C>T		intron_variant	Intron 7 of 8	ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C2	ENST00000380753.9	c.846+1070C>T		intron_variant	Intron 7 of 8	1	NM_001393392.1	ENSP00000370129.4
AKR1C2	ENST00000421196.7	c.768+1070C>T		intron_variant	Intron 6 of 7	1		ENSP00000392694.2
AKR1C2	ENST00000460124.5	n.2306+1070C>T		intron_variant	Intron 6 of 7	5

Frequencies

GnomAD3 genomes AF: 0.185 AC: 23615 AN: 127794 Hom.: 2000 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.228

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 23611 AN: 127842 Hom.: 1998 Cov.: 33 AF XY: 0.189 AC XY: 11486 AN XY: 60892

African (AFR) AF: 0.131 AC: 4375 AN: 33416

American (AMR) AF: 0.215 AC: 2430 AN: 11304

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 980 AN: 3276

East Asian (EAS) AF: 0.331 AC: 1545 AN: 4662

South Asian (SAS) AF: 0.182 AC: 645 AN: 3550

European-Finnish (FIN) AF: 0.183 AC: 1332 AN: 7272

Middle Eastern (MID) AF: 0.341 AC: 73 AN: 214

European-Non Finnish (NFE) AF: 0.190 AC: 11681 AN: 61614

Other (OTH) AF: 0.231 AC: 394 AN: 1702

Alfa AF: 0.165 Hom.: 2766

Bravo AF: 0.157

Asia WGS AF: 0.211 AC: 723 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.15
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9804392; hg19: chr10-5036441;