rs9329316

chr10-5107111-T-Cchr10-5107111-T-G

Variant summary

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

The NM_003739.6(AKR1C3):c.930-350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,052 control chromosomes in the GnomAD database, including 5,580 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 0.26 (5580 hom., cov: 32)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6	c.930-350T>C		intron_variant		ENST00000380554.5
AKR1C3	NM_001253908.2	c.930-350T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5	c.930-350T>C		intron_variant		1	NM_003739.6	P4
AKR1C3	ENST00000439082.7	c.930-350T>C		intron_variant		5		A1
AKR1C3	ENST00000605149.5	c.861-350T>C		intron_variant		2
AKR1C3	ENST00000603484.1	n.404-350T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40058 AN: 151938 Hom.: 5551 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.264 AC: 40122 AN: 152052 Hom.: 5580 Cov.: 32 AF XY: 0.261 AC XY: 19396 AN XY: 74338

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.306

Alfa AF: 0.254 Hom.: 659

Bravo AF: 0.270

Asia WGS AF: 0.256 AC: 883 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.9
Dann	Benign	0.68

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: rs9329316; hg19: chr10-5149303;