rs3209896

chr10-5107511-G-A

Variant summary

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

The NM_003739.6(AKR1C3):c.*8G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,577,388 control chromosomes in the GnomAD database, including 263,662 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 0.58 (26196 hom., cov: 31)
  • Exomes 𝑓: 0.57 (237466 hom.)
• Consequence: AKR1C3 NM_003739.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.*8G>A		3_prime_UTR_variant	9/9	ENST00000380554.5
AKR1C3	NM_001253908.2	c.*8G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.*8G>A		3_prime_UTR_variant	9/9	1	NM_003739.6	P4
AKR1C3	ENST00000605149.5	c.*8G>A		3_prime_UTR_variant	9/9	2
AKR1C3	ENST00000603484.1	n.454G>A		non_coding_transcript_exon_variant	2/2	2
AKR1C3	ENST00000439082.7			downstream_gene_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87931 AN: 151722 Hom.: 26160 Cov.: 31

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.576

GnomAD3 exomes AF: 0.516 AC: 128197 AN: 248332 Hom.: 35526 AF XY: 0.516 AC XY: 69290 AN XY: 134282

Gnomad AFR exome AF: 0.643

Gnomad AMR exome AF: 0.348

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.233

Gnomad SAS exome AF: 0.403

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.561

GnomAD4 exome AF: 0.568 AC: 810029 AN: 1425548 Hom.: 237466 Cov.: 30 AF XY: 0.564 AC XY: 401147 AN XY: 711084

Gnomad4 AFR exome AF: 0.637

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.580 AC: 88020 AN: 151840 Hom.: 26196 Cov.: 31 AF XY: 0.574 AC XY: 42601 AN XY: 74174

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.578

Alfa AF: 0.584 Hom.: 28072

Bravo AF: 0.572

Asia WGS AF: 0.356 AC: 1234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.90
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3209896; hg19: chr10-5149703; COSMIC: COSV65910051; COSMIC: COSV65910051;