chr10-5106952-A-G

Position:

• chr10-5106952-A-G

Variant summary

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

The ENST00000380554.5(AKR1C3):​c.930-509A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 151,990 control chromosomes in the GnomAD database, including 46,427 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 0.78 (46427 hom., cov: 31)
• Consequence: AKR1C3 ENST00000380554.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.930-509A>G		intron_variant		ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.930-509A>G		intron_variant			NP_001240837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.930-509A>G		intron_variant		1	NM_003739.6	ENSP00000369927	P4
AKR1C3	ENST00000439082.7	c.930-509A>G		intron_variant		5		ENSP00000401327	A1
AKR1C3	ENST00000605149.5	c.861-509A>G		intron_variant		2		ENSP00000474882
AKR1C3	ENST00000603484.1	n.404-509A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118496 AN: 151872 Hom.: 46378 Cov.: 31

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.780 AC: 118600 AN: 151990 Hom.: 46427 Cov.: 31 AF XY: 0.780 AC XY: 57943 AN XY: 74272

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.807

Alfa AF: 0.696 Hom.: 2127

Bravo AF: 0.783

Asia WGS AF: 0.853 AC: 2962 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.49

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: rs4242785; hg19: chr10-5149144;