10-5102986-A-G

Variant names:

• chr10-5102986-A-G
• rs12775701
• NM_003739.6:c.846+336A>G

Variant summary

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

The NM_003739.6(AKR1C3):​c.846+336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 150,490 control chromosomes in the GnomAD database, including 20,478 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 0.51 (20478 hom., cov: 28)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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.846+336A>G		intron	N/A	NP_003730.4
	AKR1C3	NM_001253908.2		c.846+336A>G		intron	N/A	NP_001240837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C3	ENST00000380554.5	TSL:1 MANE Select	c.846+336A>G		intron	N/A	ENSP00000369927.3
	AKR1C3	ENST00000439082.7	TSL:5	c.846+336A>G		intron	N/A	ENSP00000401327.3
	AKR1C3	ENST00000605149.5	TSL:2	c.777+336A>G		intron	N/A	ENSP00000474882.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 77382 AN: 150386 Hom.: 20464 Cov.: 28

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.515 AC: 77434 AN: 150490 Hom.: 20478 Cov.: 28 AF XY: 0.516 AC XY: 37898 AN XY: 73382

African (AFR) AF: 0.516 AC: 21135 AN: 40970

American (AMR) AF: 0.558 AC: 8461 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2257 AN: 3470

East Asian (EAS) AF: 0.863 AC: 4419 AN: 5118

South Asian (SAS) AF: 0.666 AC: 3168 AN: 4760

European-Finnish (FIN) AF: 0.430 AC: 4332 AN: 10086

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31720 AN: 67640

Other (OTH) AF: 0.595 AC: 1247 AN: 2096

Alfa AF: 0.327 Hom.: 800

Bravo AF: 0.526

Asia WGS AF: 0.749 AC: 2602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.5
DANN	Benign	0.24
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12775701; hg19: chr10-5145178;