rs1937841

chr10-5099097-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003739.6(AKR1C3):c.447+218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 152,224 control chromosomes in the GnomAD database, including 683 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 0.087 (683 hom., cov: 32)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.447+218G>A		intron_variant		ENST00000380554.5
AKR1C3	NM_001253908.2	c.447+218G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.447+218G>A		intron_variant		1	NM_003739.6	P4

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13179 AN: 152106 Hom.: 680 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0661

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

GnomAD4 genome AF: 0.0866 AC: 13187 AN: 152224 Hom.: 683 Cov.: 32 AF XY: 0.0906 AC XY: 6743 AN XY: 74428

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0943 Hom.: 117

Bravo AF: 0.0837

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.31
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1937841; hg19: chr10-5141289; COSMIC: COSV65911002; COSMIC: COSV65911002;