rs2275928

Positions:

• chr10-5105717-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.929+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,515,468 control chromosomes in the GnomAD database, including 255,408 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 (26266 hom., cov: 31)
  • Exomes 𝑓: 0.57 (229142 hom.)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.929+40G>A		intron_variant		ENST00000380554.5
AKR1C3	NM_001253908.2	c.929+40G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.929+40G>A		intron_variant		1	NM_003739.6	P4
AKR1C3	ENST00000439082.7	c.929+40G>A		intron_variant		5		A1
AKR1C3	ENST00000605149.5	c.860+40G>A		intron_variant		2
AKR1C3	ENST00000603484.1	n.403+40G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88141 AN: 151944 Hom.: 26230 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.577

GnomAD3 exomes AF: 0.519 AC: 117209 AN: 225638 Hom.: 32339 AF XY: 0.519 AC XY: 62958 AN XY: 121316

Gnomad AFR exome AF: 0.646

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.502

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.417

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.571 AC: 778970 AN: 1363406 Hom.: 229142 Cov.: 19 AF XY: 0.567 AC XY: 386751 AN XY: 681820

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.638

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.580 AC: 88229 AN: 152062 Hom.: 26266 Cov.: 31 AF XY: 0.575 AC XY: 42734 AN XY: 74310

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.579

Alfa AF: 0.589 Hom.: 28078

Bravo AF: 0.572

Asia WGS AF: 0.364 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2275928; hg19: chr10-5147909; COSMIC: COSV65910185; COSMIC: COSV65910185;