rs2518049

Variant names:

• chr10-5095844-A-G
• rs2518049
• NM_003739.6:c.85-566A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.85-566A>G		intron_variant	Intron 1 of 8	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.85-566A>G		intron_variant	Intron 1 of 8		NP_001240837.1
AKR1C3	NM_001253909.2	c.85-566A>G		intron_variant	Intron 1 of 2		NP_001240838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.85-566A>G		intron_variant	Intron 1 of 8	1	NM_003739.6	ENSP00000369927.3

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

African (AFR) AF: 0.963 AC: 39986 AN: 41540

American (AMR) AF: 0.828 AC: 12629 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3082 AN: 3470

East Asian (EAS) AF: 0.867 AC: 4479 AN: 5164

South Asian (SAS) AF: 0.868 AC: 4181 AN: 4818

European-Finnish (FIN) AF: 0.829 AC: 8771 AN: 10582

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56477 AN: 67962

Other (OTH) AF: 0.893 AC: 1885 AN: 2112

Alfa AF: 0.842 Hom.: 164941

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
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2518049; hg19: chr10-5138036;