chr10-4993054-C-T

Variant names:

• chr10-4993054-C-T
• rs10904387
• NM_001393392.1:c.847-1141G>A

Variant summary

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

The NM_001393392.1(AKR1C2):​c.847-1141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,074 control chromosomes in the GnomAD database, including 7,015 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 0.29 (7015 hom., cov: 33)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 2 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393392.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C2	NM_001393392.1	MANE Select	c.847-1141G>A		intron	N/A	NP_001380321.1	P52895-1
	AKR1C2	NM_001354.6		c.847-1141G>A		intron	N/A	NP_001345.1	P52895-1
	AKR1C2	NM_205845.3		c.847-1141G>A		intron	N/A	NP_995317.1	P52895-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C2	ENST00000380753.9	TSL:1 MANE Select	c.847-1141G>A		intron	N/A	ENSP00000370129.4	P52895-1
	AKR1C2	ENST00000421196.7	TSL:1	c.769-1141G>A		intron	N/A	ENSP00000392694.2	B4DK69
	AKR1C2	ENST00000867375.1		c.970-1141G>A		intron	N/A	ENSP00000537434.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43691 AN: 151956 Hom.: 7015 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.287 AC: 43705 AN: 152074 Hom.: 7015 Cov.: 33 AF XY: 0.296 AC XY: 22018 AN XY: 74320

African (AFR) AF: 0.197 AC: 8184 AN: 41482

American (AMR) AF: 0.381 AC: 5814 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3250 AN: 5172

South Asian (SAS) AF: 0.515 AC: 2484 AN: 4822

European-Finnish (FIN) AF: 0.264 AC: 2786 AN: 10552

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19164 AN: 67988

Other (OTH) AF: 0.307 AC: 648 AN: 2114

Alfa AF: 0.284 Hom.: 19604

Bravo AF: 0.292

Asia WGS AF: 0.480 AC: 1664 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.20
PhyloP100		-0.068
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: rs10904387; hg19: chr10-5035246;