NM_001253908.2:c.85-19757C>T

Variant names:

• chr10-5076653-C-T
• rs10752001
• NM_001253908.2:c.85-19757C>T

Variant summary

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

The NM_001253908.2(AKR1C3):​c.85-19757C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 151,940 control chromosomes in the GnomAD database, including 55,597 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 0.85 (55597 hom., cov: 32)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_001253908.2	c.85-19757C>T		intron_variant	Intron 1 of 8		NP_001240837.1
LOC107984198	XR_001747341.2	n.717-1247C>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000439082.7	c.85-19757C>T		intron_variant	Intron 1 of 8	5		ENSP00000401327.3
AKR1C3	ENST00000602997.5	c.-63-1247C>T		intron_variant	Intron 1 of 5	3		ENSP00000474188.1
AKR1C3	ENST00000470862.6	n.261-1217C>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129745 AN: 151822 Hom.: 55543 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.855 AC: 129858 AN: 151940 Hom.: 55597 Cov.: 32 AF XY: 0.854 AC XY: 63378 AN XY: 74230

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.845

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.827

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.882

Alfa AF: 0.836 Hom.: 68453

Bravo AF: 0.859

Asia WGS AF: 0.875 AC: 3044 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	0.49
DANN	Benign	0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10752001; hg19: chr10-5118845;