chr10-5093021-T-C

Variant names:

• chr10-5093021-T-C
• rs11252937
• NM_001253908.2:c.85-3389T>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.85-3389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,906 control chromosomes in the GnomAD database, including 8,556 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 0.32 (8556 hom., cov: 32)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_001253908.2	c.85-3389T>C		intron_variant	Intron 1 of 8		NP_001240837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000439082.7	c.85-3389T>C		intron_variant	Intron 1 of 8	5		ENSP00000401327.3
AKR1C3	ENST00000605149.5	c.16-3389T>C		intron_variant	Intron 1 of 8	2		ENSP00000474882.1
AKR1C3	ENST00000602997.5	c.16-3389T>C		intron_variant	Intron 2 of 5	3		ENSP00000474188.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49224 AN: 151788 Hom.: 8549 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.324 AC: 49265 AN: 151906 Hom.: 8556 Cov.: 32 AF XY: 0.323 AC XY: 23946 AN XY: 74244

African (AFR) AF: 0.333 AC: 13801 AN: 41422

American (AMR) AF: 0.255 AC: 3880 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3466

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5170

South Asian (SAS) AF: 0.183 AC: 884 AN: 4822

European-Finnish (FIN) AF: 0.404 AC: 4268 AN: 10556

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24638 AN: 67938

Other (OTH) AF: 0.278 AC: 585 AN: 2106

Alfa AF: 0.343 Hom.: 1154

Bravo AF: 0.311

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.73
PhyloP100		0.73
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: rs11252937; hg19: chr10-5135213;