rs1937845

chr10-5093956-A-G

Variant summary

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

The NM_001253908.2(AKR1C3):c.85-2454A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,922 control chromosomes in the GnomAD database, including 16,664 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 0.46 (16663 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_001253908.2	c.85-2454A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000439082.7	c.85-2454A>G		intron_variant		5		A1
AKR1C3	ENST00000602997.5	c.16-2454A>G		intron_variant		3
AKR1C3	ENST00000605149.5	c.16-2454A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69130 AN: 151796 Hom.: 16644 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.455 AC: 69186 AN: 151916 Hom.: 16663 Cov.: 33 AF XY: 0.457 AC XY: 33937 AN XY: 74252

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.862

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.525

Alfa AF: 0.427 Hom.: 2369

Bravo AF: 0.472

Asia WGS AF: 0.744 AC: 2563 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.4
Dann	Benign	0.43

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: rs1937845; hg19: chr10-5136148;