NM_001253908.2:c.85-20280A>C

Variant names:

• chr10-5076130-A-C
• rs6601899
• NM_001253908.2:c.85-20280A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001253908.2(AKR1C3):​c.85-20280A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,164 control chromosomes in the GnomAD database, including 58,012 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 (58012 hom., cov: 31)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 3 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]

LOC107984198 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_001253908.2	c.85-20280A>C		intron_variant	Intron 1 of 8		NP_001240837.1
LOC107984198	XR_001747341.2	n.717-1770A>C		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000439082.7	c.85-20280A>C		intron_variant	Intron 1 of 8	5		ENSP00000401327.3
AKR1C3	ENST00000602997.5	c.-63-1770A>C		intron_variant	Intron 1 of 5	3		ENSP00000474188.1
AKR1C3	ENST00000470862.6	n.261-1740A>C		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132470 AN: 152046 Hom.: 57952 Cov.: 31

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.871 AC: 132589 AN: 152164 Hom.: 58012 Cov.: 31 AF XY: 0.870 AC XY: 64742 AN XY: 74382

African (AFR) AF: 0.959 AC: 39841 AN: 41530

American (AMR) AF: 0.851 AC: 13010 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2984 AN: 3468

East Asian (EAS) AF: 0.880 AC: 4550 AN: 5170

South Asian (SAS) AF: 0.862 AC: 4155 AN: 4820

European-Finnish (FIN) AF: 0.829 AC: 8760 AN: 10570

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56330 AN: 68002

Other (OTH) AF: 0.893 AC: 1888 AN: 2114

Alfa AF: 0.848 Hom.: 82470

Bravo AF: 0.877

Asia WGS AF: 0.890 AC: 3095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.28
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6601899; hg19: chr10-5118322;