rs28943575

Positions:

• chr10-5071378-G-C

Variant summary

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

The XR_007062039.1(LOC124902366):​n.1592C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,204 control chromosomes in the GnomAD database, including 609 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 0.075 (609 hom., cov: 32)
• Consequence: LOC124902366 XR_007062039.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636

Genes affected

LOC124902366 (HGNC:):

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902366	XR_007062039.1	n.1592C>G		non_coding_transcript_exon_variant	1/2
LOC107984198	XR_001747341.2	n.717-6522G>C		intron_variant, non_coding_transcript_variant
AKR1C3	NM_001253908.2	c.84+22483G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000439082.7	c.84+22483G>C		intron_variant		5		A1
AKR1C3	ENST00000602997.5	c.-63-6522G>C		intron_variant		3
AKR1C3	ENST00000470862.6	n.261-6492G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11483 AN: 152086 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0708

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

GnomAD4 genome AF: 0.0754 AC: 11483 AN: 152204 Hom.: 609 Cov.: 32 AF XY: 0.0732 AC XY: 5445 AN XY: 74418

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.0680

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0927 Hom.: 98

Bravo AF: 0.0719

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28943575; hg19: chr10-5113570;