rs10508293

chr10-5098945-A-Gchr10-5098945-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.447+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,301,388 control chromosomes in the GnomAD database, including 39,366 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 0.20 (4063 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35303 hom.)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.447+66A>G		intron_variant		ENST00000380554.5
AKR1C3	NM_001253908.2	c.447+66A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.447+66A>G		intron_variant		1	NM_003739.6	P4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30170 AN: 152054 Hom.: 4065 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.213 AC: 244905 AN: 1149216 Hom.: 35303 AF XY: 0.219 AC XY: 127563 AN XY: 581540

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.198 AC: 30174 AN: 152172 Hom.: 4063 Cov.: 32 AF XY: 0.205 AC XY: 15214 AN XY: 74380

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.227

Alfa AF: 0.192 Hom.: 1493

Bravo AF: 0.210

Asia WGS AF: 0.512 AC: 1781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.7
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10508293; hg19: chr10-5141137;