rs7741

chr10-5096415-G-Achr10-5096415-G-Cchr10-5096415-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003739.6(AKR1C3):c.90G>A(p.Pro30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,612,162 control chromosomes in the GnomAD database, including 96,429 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 0.32 (8461 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87968 hom.)
• Consequence: AKR1C3 NM_003739.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-2.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.90G>A	p.Pro30=	synonymous_variant	2/9	ENST00000380554.5
AKR1C3	NM_001253908.2	c.90G>A	p.Pro30=	synonymous_variant	2/9
AKR1C3	NM_001253909.2	c.90G>A	p.Pro30=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.90G>A	p.Pro30=	synonymous_variant	2/9	1	NM_003739.6	P4

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48941 AN: 151886 Hom.: 8454 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.280 AC: 70005 AN: 250292 Hom.: 11547 AF XY: 0.279 AC XY: 37730 AN XY: 135210

Gnomad AFR exome AF: 0.333

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.00191

Gnomad SAS exome AF: 0.181

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.336 AC: 490762 AN: 1460158 Hom.: 87968 Cov.: 34 AF XY: 0.332 AC XY: 240913 AN XY: 726318

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.00270

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.322 AC: 48984 AN: 152004 Hom.: 8461 Cov.: 32 AF XY: 0.320 AC XY: 23813 AN XY: 74320

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.278

Alfa AF: 0.313 Hom.: 4817

Bravo AF: 0.309

Asia WGS AF: 0.0980 AC: 341 AN: 3478

EpiCase AF: 0.347

EpiControl AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.6
Dann	Benign	0.85

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: rs7741; hg19: chr10-5138607; COSMIC: COSV65910364; COSMIC: COSV65910364;