rs1937841

Variant names:

• chr10-5099097-G-A
• rs1937841
• NM_003739.6:c.447+218G>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.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
• Publications: 5 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=-0.9).
• 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 rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.447+218G>A		intron_variant	Intron 4 of 8	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.447+218G>A		intron_variant	Intron 4 of 8		NP_001240837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.447+218G>A		intron_variant	Intron 4 of 8	1	NM_003739.6	ENSP00000369927.3

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

African (AFR) AF: 0.0207 AC: 860 AN: 41524

American (AMR) AF: 0.135 AC: 2067 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3472

East Asian (EAS) AF: 0.132 AC: 685 AN: 5174

South Asian (SAS) AF: 0.119 AC: 574 AN: 4826

European-Finnish (FIN) AF: 0.130 AC: 1383 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7211 AN: 68014

Other (OTH) AF: 0.0659 AC: 139 AN: 2110

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
PhyloP100		-1.5
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: rs1937841; hg19: chr10-5141289; COSMIC: COSV65911002; COSMIC: COSV65911002;