rs11252946

chr10-5104377-A-Gchr10-5104377-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.847-1218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 105,004 control chromosomes in the GnomAD database, including 5,395 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 0.38 (5395 hom., cov: 32)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.847-1218A>G		intron_variant		ENST00000380554.5
AKR1C3	NM_001253908.2	c.847-1218A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.847-1218A>G		intron_variant		1	NM_003739.6	P4
AKR1C3	ENST00000439082.7	c.847-1218A>G		intron_variant		5		A1
AKR1C3	ENST00000605149.5	c.778-1218A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 39595 AN: 104920 Hom.: 5381 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.479

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.378 AC: 39640 AN: 105004 Hom.: 5395 Cov.: 32 AF XY: 0.375 AC XY: 19098 AN XY: 50954

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.449

Alfa AF: 0.252 Hom.: 623

Bravo AF: 0.267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.76
Dann	Benign	0.42

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: rs11252946; hg19: chr10-5146569;