10-5101871-C-G

Variant names:

• chr10-5101871-C-G
• rs12242350
• NM_003739.6:c.571-230C>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.571-230C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,830 control chromosomes in the GnomAD database, including 4,872 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 (4872 hom., cov: 33)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.571-230C>G		intron_variant	Intron 5 of 8	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.571-230C>G		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.571-230C>G		intron_variant	Intron 5 of 8	1	NM_003739.6	ENSP00000369927.3
AKR1C3	ENST00000439082.7	c.571-230C>G		intron_variant	Intron 5 of 8	5		ENSP00000401327.3
AKR1C3	ENST00000605149.5	c.502-230C>G		intron_variant	Intron 5 of 8	2		ENSP00000474882.1
AKR1C3	ENST00000605781.5	n.750-230C>G		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37962 AN: 151712 Hom.: 4859 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.250 AC: 38002 AN: 151830 Hom.: 4872 Cov.: 33 AF XY: 0.247 AC XY: 18332 AN XY: 74198

African (AFR) AF: 0.286 AC: 11837 AN: 41356

American (AMR) AF: 0.232 AC: 3544 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3466

East Asian (EAS) AF: 0.231 AC: 1193 AN: 5164

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4814

European-Finnish (FIN) AF: 0.223 AC: 2350 AN: 10526

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16083 AN: 67920

Other (OTH) AF: 0.298 AC: 627 AN: 2104

Alfa AF: 0.247 Hom.: 587

Bravo AF: 0.255

Asia WGS AF: 0.254 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.75
DANN	Benign	0.39
PhyloP100		-1.0
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: rs12242350; hg19: chr10-5144063;