rs2518049

Positions:

• chr10-5095844-A-G
• chr10-5095844-A-T

Variant summary

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

The NM_003739.6(AKR1C3):​c.85-566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,104 control chromosomes in the GnomAD database, including 58,019 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 0.87 (58019 hom., cov: 31)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.85-566A>G		intron_variant		ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.85-566A>G		intron_variant			NP_001240837.1
AKR1C3	NM_001253909.2	c.85-566A>G		intron_variant			NP_001240838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.85-566A>G		intron_variant		1	NM_003739.6	ENSP00000369927	P4

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132451 AN: 151986 Hom.: 57962 Cov.: 31

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.892

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.872 AC: 132564 AN: 152104 Hom.: 58019 Cov.: 31 AF XY: 0.870 AC XY: 64662 AN XY: 74350

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.893

Alfa AF: 0.836 Hom.: 52822

Bravo AF: 0.875

Asia WGS AF: 0.885 AC: 3078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.57

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: rs2518049; hg19: chr10-5138036;