rs1937843

Positions:

• chr10-5094723-A-G
• chr10-5094723-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003739.6(AKR1C3):​c.84+195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,772 control chromosomes in the GnomAD database, including 8,593 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 0.33 (8593 hom., cov: 31)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

Genes affected

AKR1C3 (HGNC:386): (aldo-keto reductase family 1 member C3) 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 by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. 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 different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.84+195A>G		intron_variant		ENST00000380554.5
AKR1C3	NM_001253908.2	c.85-1687A>G		intron_variant
AKR1C3	NM_001253909.2	c.84+195A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.84+195A>G		intron_variant		1	NM_003739.6	P4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49337 AN: 151654 Hom.: 8585 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.325 AC: 49382 AN: 151772 Hom.: 8593 Cov.: 31 AF XY: 0.324 AC XY: 23991 AN XY: 74158

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.00329

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.279

Alfa AF: 0.340 Hom.: 1790

Bravo AF: 0.312

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.29

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: rs1937843; hg19: chr10-5136915;