rs11597709

Variant names:

• chr10-5080234-G-A
• rs11597709
• NM_001253908.2:c.85-16176G>A

Variant summary

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

The NM_001253908.2(AKR1C3):​c.85-16176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 152,238 control chromosomes in the GnomAD database, including 194 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 0.049 (194 hom., cov: 33)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• 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]

LOC107984198 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_001253908.2	c.85-16176G>A		intron_variant	Intron 1 of 8		NP_001240837.1
LOC107984198	XR_001747341.2	n.795-512G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000439082.7	c.85-16176G>A		intron_variant	Intron 1 of 8	5		ENSP00000401327.3
AKR1C3	ENST00000605149.5	c.15+2257G>A		intron_variant	Intron 1 of 8	2		ENSP00000474882.1
AKR1C3	ENST00000602997.5	c.15+2257G>A		intron_variant	Intron 2 of 5	3		ENSP00000474188.1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7502 AN: 152120 Hom.: 195 Cov.: 33

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0492 AC: 7497 AN: 152238 Hom.: 194 Cov.: 33 AF XY: 0.0471 AC XY: 3507 AN XY: 74442

African (AFR) AF: 0.0246 AC: 1022 AN: 41544

American (AMR) AF: 0.0479 AC: 732 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.0232 AC: 120 AN: 5172

South Asian (SAS) AF: 0.0396 AC: 191 AN: 4820

European-Finnish (FIN) AF: 0.0304 AC: 323 AN: 10612

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4609 AN: 68006

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0597 Hom.: 517

Bravo AF: 0.0492

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.60
PhyloP100		0.022
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: rs11597709; hg19: chr10-5122426;