10-5101845-T-G

Variant names:

• chr10-5101845-T-G
• rs4881400
• NM_003739.6:c.571-256T>G

Variant summary

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

The NM_003739.6(AKR1C3):​c.571-256T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,092 control chromosomes in the GnomAD database, including 5,745 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 (5745 hom., cov: 32)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.571-256T>G		intron_variant	Intron 5 of 8	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.571-256T>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.571-256T>G		intron_variant	Intron 5 of 8	1	NM_003739.6	ENSP00000369927.3
AKR1C3	ENST00000439082.7	c.571-256T>G		intron_variant	Intron 5 of 8	5		ENSP00000401327.3
AKR1C3	ENST00000605149.5	c.502-256T>G		intron_variant	Intron 5 of 8	2		ENSP00000474882.1
AKR1C3	ENST00000605781.5	n.750-256T>G		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38984 AN: 151976 Hom.: 5750 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.256 AC: 38990 AN: 152092 Hom.: 5745 Cov.: 32 AF XY: 0.262 AC XY: 19475 AN XY: 74360

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.293

Alfa AF: 0.244 Hom.: 10058

Bravo AF: 0.267

Asia WGS AF: 0.508 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.86

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: rs4881400; hg19: chr10-5144037;