rs10795241

Positions:

• chr10-5062098-T-C

Variant summary

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

The NM_001253908.2(AKR1C3):​c.84+13203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,052 control chromosomes in the GnomAD database, including 7,685 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 0.31 (7685 hom., cov: 32)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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]

AKR1C3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C3	NM_001253908.2	c.84+13203T>C		intron_variant			NP_001240837.1
LOC107984198	XR_001747341.2	n.717-15802T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000439082.7	c.84+13203T>C		intron_variant		5		ENSP00000401327.3
AKR1C3	ENST00000602997.5	c.-64+13203T>C		intron_variant		3		ENSP00000474188.1
AKR1C3	ENST00000470862.6	n.261-15772T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47727 AN: 151934 Hom.: 7680 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.314 AC: 47764 AN: 152052 Hom.: 7685 Cov.: 32 AF XY: 0.311 AC XY: 23087 AN XY: 74342

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.327

Alfa AF: 0.295 Hom.: 9451

Bravo AF: 0.318

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.91
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10795241; hg19: chr10-5104290;