rs2245191

chr10-5097623-C-Achr10-5097623-C-Gchr10-5097623-C-T

Variant summary

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

The NM_003739.6(AKR1C3):c.369+73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,605,368 control chromosomes in the GnomAD database, including 43,723 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 0.25 (4909 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38814 hom.)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.369+73C>A		intron_variant		ENST00000380554.5
AKR1C3	NM_001253909.2	c.*25C>A		3_prime_UTR_variant	3/3
AKR1C3	NM_001253908.2	c.369+73C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.369+73C>A		intron_variant		1	NM_003739.6	P4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37819 AN: 151868 Hom.: 4896 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.283

GnomAD3 exomes AF: 0.224 AC: 55830 AN: 249040 Hom.: 6520 AF XY: 0.226 AC XY: 30387 AN XY: 134700

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.255

Gnomad EAS exome AF: 0.207

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.228 AC: 331523 AN: 1453382 Hom.: 38814 Cov.: 36 AF XY: 0.228 AC XY: 165113 AN XY: 723108

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.249 AC: 37864 AN: 151986 Hom.: 4909 Cov.: 32 AF XY: 0.245 AC XY: 18194 AN XY: 74296

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.289

Alfa AF: 0.197 Hom.: 975

Bravo AF: 0.252

Asia WGS AF: 0.233 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.6
Dann	Benign	0.61

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: rs2245191; hg19: chr10-5139815; COSMIC: COSV65910181; COSMIC: COSV65910181;