rs4344395

Variant names:

• chr10-4993486-A-T
• rs4344395
• NM_001393392.1:c.847-1573T>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.847-1573T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,568 control chromosomes in the GnomAD database, including 14,821 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 0.43 (14821 hom., cov: 33)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C2	NM_001393392.1	c.847-1573T>A		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.847-1573T>A		intron_variant	Intron 7 of 8	1	NM_001393392.1	ENSP00000370129.4
AKR1C2	ENST00000421196.7	c.769-1573T>A		intron_variant	Intron 6 of 7	1		ENSP00000392694.2
AKR1C2	ENST00000460124.5	n.2307-1573T>A		intron_variant	Intron 6 of 7	5

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64585 AN: 151450 Hom.: 14818 Cov.: 33

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.426 AC: 64633 AN: 151568 Hom.: 14821 Cov.: 33 AF XY: 0.423 AC XY: 31299 AN XY: 74030

African (AFR) AF: 0.333 AC: 13766 AN: 41384

American (AMR) AF: 0.398 AC: 6073 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3466

East Asian (EAS) AF: 0.0615 AC: 319 AN: 5188

South Asian (SAS) AF: 0.325 AC: 1563 AN: 4816

European-Finnish (FIN) AF: 0.577 AC: 6014 AN: 10426

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34345 AN: 67734

Other (OTH) AF: 0.400 AC: 843 AN: 2106

Alfa AF: 0.471 Hom.: 2165

Bravo AF: 0.410

Asia WGS AF: 0.256 AC: 888 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.30
PhyloP100		-0.12
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: rs4344395; hg19: chr10-5035678;