10-5096415-G-A

Variant names:

• chr10-5096415-G-A
• rs7741
• NM_003739.6:c.90G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003739.6(AKR1C3):​c.90G>A​(p.Pro30Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,612,162 control chromosomes in the GnomAD database, including 96,429 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 (8461 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87968 hom.)
• Consequence: AKR1C3 NM_003739.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 20 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-2.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003739.6. 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_003739.6	MANE Select	c.90G>A	p.Pro30Pro	synonymous	Exon 2 of 9	NP_003730.4
	AKR1C3	NM_001253908.2		c.90G>A	p.Pro30Pro	synonymous	Exon 2 of 9	NP_001240837.1
	AKR1C3	NM_001253909.2		c.90G>A	p.Pro30Pro	synonymous	Exon 2 of 3	NP_001240838.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C3	ENST00000380554.5	TSL:1 MANE Select	c.90G>A	p.Pro30Pro	synonymous	Exon 2 of 9	ENSP00000369927.3
	AKR1C3	ENST00000480697.6	TSL:1	n.121G>A		non_coding_transcript_exon	Exon 2 of 3
	AKR1C3	ENST00000605322.1	TSL:1	n.117G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48941 AN: 151886 Hom.: 8454 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.281

GnomAD2 exomes AF: 0.280 AC: 70005 AN: 250292 AF XY: 0.279

Gnomad AFR exome AF: 0.333

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.00191

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.336 AC: 490762 AN: 1460158 Hom.: 87968 Cov.: 34 AF XY: 0.332 AC XY: 240913 AN XY: 726318

African (AFR) AF: 0.320 AC: 10671 AN: 33368

American (AMR) AF: 0.172 AC: 7678 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6329 AN: 26040

East Asian (EAS) AF: 0.00270 AC: 107 AN: 39674

South Asian (SAS) AF: 0.184 AC: 15860 AN: 86054

European-Finnish (FIN) AF: 0.405 AC: 21591 AN: 53340

Middle Eastern (MID) AF: 0.186 AC: 1069 AN: 5752

European-Non Finnish (NFE) AF: 0.368 AC: 408771 AN: 1110928

Other (OTH) AF: 0.310 AC: 18686 AN: 60330

GnomAD4 genome AF: 0.322 AC: 48984 AN: 152004 Hom.: 8461 Cov.: 32 AF XY: 0.320 AC XY: 23813 AN XY: 74320

African (AFR) AF: 0.329 AC: 13660 AN: 41472

American (AMR) AF: 0.254 AC: 3881 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 824 AN: 3468

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5178

South Asian (SAS) AF: 0.165 AC: 795 AN: 4816

European-Finnish (FIN) AF: 0.405 AC: 4270 AN: 10552

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

European-Non Finnish (NFE) AF: 0.362 AC: 24584 AN: 67938

Other (OTH) AF: 0.278 AC: 586 AN: 2110

Alfa AF: 0.320 Hom.: 6775

Bravo AF: 0.309

Asia WGS AF: 0.0980 AC: 341 AN: 3478

EpiCase AF: 0.347

EpiControl AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.85
PhyloP100		-2.5
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7741; hg19: chr10-5138607; COSMIC: COSV65910364; COSMIC: COSV65910364;