ENST00000480697.6:n.473C>A

Variant names:

• chr10-5097623-C-A
• rs2245191
• ENST00000480697.6:n.473C>A

Variant summary

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

The ENST00000480697.6(AKR1C3):​n.473C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,605,368 control chromosomes in the GnomAD database, including 43,723 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 0.25 (4909 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38814 hom.)
• Consequence: AKR1C3 ENST00000480697.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.369+73C>A		intron_variant	Intron 3 of 8	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253909.2	c.*25C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001240838.1
AKR1C3	NM_001253908.2	c.369+73C>A		intron_variant	Intron 3 of 8		NP_001240837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.369+73C>A		intron_variant	Intron 3 of 8	1	NM_003739.6	ENSP00000369927.3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37819 AN: 151868 Hom.: 4896 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.283

GnomAD2 exomes AF: 0.224 AC: 55830 AN: 249040 AF XY: 0.226

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.255

Gnomad EAS exome AF: 0.207

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.228 AC: 331523 AN: 1453382 Hom.: 38814 Cov.: 36 AF XY: 0.228 AC XY: 165113 AN XY: 723108

African (AFR) AF: 0.319 AC: 10602 AN: 33200

American (AMR) AF: 0.156 AC: 6908 AN: 44280

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6686 AN: 25874

East Asian (EAS) AF: 0.170 AC: 6681 AN: 39250

South Asian (SAS) AF: 0.213 AC: 18259 AN: 85776

European-Finnish (FIN) AF: 0.228 AC: 11989 AN: 52488

Middle Eastern (MID) AF: 0.373 AC: 2138 AN: 5730

European-Non Finnish (NFE) AF: 0.229 AC: 253463 AN: 1106922

Other (OTH) AF: 0.247 AC: 14797 AN: 59862

GnomAD4 genome AF: 0.249 AC: 37864 AN: 151986 Hom.: 4909 Cov.: 32 AF XY: 0.245 AC XY: 18194 AN XY: 74296

African (AFR) AF: 0.308 AC: 12772 AN: 41440

American (AMR) AF: 0.200 AC: 3053 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1064 AN: 5162

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4810

European-Finnish (FIN) AF: 0.221 AC: 2332 AN: 10562

Middle Eastern (MID) AF: 0.359 AC: 104 AN: 290

European-Non Finnish (NFE) AF: 0.231 AC: 15711 AN: 67972

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.199 Hom.: 1014

Bravo AF: 0.252

Asia WGS AF: 0.233 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-0.51
Mutation Taster		=100/0	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: rs2245191; hg19: chr10-5139815; COSMIC: COSV65910181; COSMIC: COSV65910181;