NM_003739.6:c.570+1214C>A

Variant names:

• chr10-5100663-C-A
• rs4559587
• NM_003739.6:c.570+1214C>A

Variant summary

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

The NM_003739.6(AKR1C3):​c.570+1214C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 152,336 control chromosomes in the GnomAD database, including 69,944 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 0.96 (69944 hom., cov: 33)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.570+1214C>A		intron_variant	Intron 5 of 8	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.570+1214C>A		intron_variant	Intron 5 of 8		NP_001240837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.570+1214C>A		intron_variant	Intron 5 of 8	1	NM_003739.6	ENSP00000369927.3
AKR1C3	ENST00000439082.7	c.570+1214C>A		intron_variant	Intron 5 of 8	5		ENSP00000401327.3
AKR1C3	ENST00000605149.5	c.501+1214C>A		intron_variant	Intron 5 of 8	2		ENSP00000474882.1
AKR1C3	ENST00000605781.5	n.749+1214C>A		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145779 AN: 152218 Hom.: 69882 Cov.: 33

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.958 AC: 145901 AN: 152336 Hom.: 69944 Cov.: 33 AF XY: 0.960 AC XY: 71497 AN XY: 74488

African (AFR) AF: 0.982 AC: 40846 AN: 41576

American (AMR) AF: 0.962 AC: 14729 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3253 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5185 AN: 5186

South Asian (SAS) AF: 0.987 AC: 4768 AN: 4830

European-Finnish (FIN) AF: 0.959 AC: 10185 AN: 10620

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63740 AN: 68030

Other (OTH) AF: 0.958 AC: 2023 AN: 2112

Alfa AF: 0.940 Hom.: 103979

Bravo AF: 0.959

Asia WGS AF: 0.988 AC: 3432 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.15
PhyloP100		-0.42
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: rs4559587; hg19: chr10-5142855;