rs28942669

Variant names:

• chr10-5092812-C-T
• rs28942669
• NM_001253908.2:c.85-3598C>T

Variant summary

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

The NM_001253908.2(AKR1C3):​c.85-3598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0627 in 152,044 control chromosomes in the GnomAD database, including 350 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 0.063 (350 hom., cov: 32)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253908.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C3	NM_001253908.2		c.85-3598C>T		intron	N/A	NP_001240837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C3	ENST00000439082.7	TSL:5	c.85-3598C>T		intron	N/A	ENSP00000401327.3
	AKR1C3	ENST00000605149.5	TSL:2	c.16-3598C>T		intron	N/A	ENSP00000474882.1
	AKR1C3	ENST00000602997.5	TSL:3	c.16-3598C>T		intron	N/A	ENSP00000474188.1

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9519 AN: 151926 Hom.: 349 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0698

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

GnomAD4 genome AF: 0.0627 AC: 9528 AN: 152044 Hom.: 350 Cov.: 32 AF XY: 0.0620 AC XY: 4606 AN XY: 74326

African (AFR) AF: 0.0587 AC: 2435 AN: 41510

American (AMR) AF: 0.0582 AC: 887 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0551 AC: 191 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5158

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4832

European-Finnish (FIN) AF: 0.0931 AC: 985 AN: 10576

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0692 AC: 4705 AN: 67950

Other (OTH) AF: 0.0690 AC: 145 AN: 2100

Alfa AF: 0.0730 Hom.: 65

Bravo AF: 0.0609

Asia WGS AF: 0.0130 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs28942669; hg19: chr10-5135004;