10-4967172-T-C

Position:

• chr10-4967172-T-C

Variant summary

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

The NM_001353.6(AKR1C1):​c.369+129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,097,164 control chromosomes in the GnomAD database, including 251,262 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 0.69 (36500 hom., cov: 33)
  • Exomes 𝑓: 0.67 (214762 hom.)
• Consequence: AKR1C1 NM_001353.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

Genes affected

AKR1C1 (HGNC:384): (aldo-keto reductase family 1 member C1) 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 reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]

AKR1C1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C1	NM_001353.6	c.369+129T>C		intron_variant		ENST00000380872.9	NP_001344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C1	ENST00000380872.9	c.369+129T>C		intron_variant		1	NM_001353.6	ENSP00000370254.4
AKR1C1	ENST00000442997.5	c.267+129T>C		intron_variant		3		ENSP00000416415.1
AKR1C1	ENST00000380859.1	c.375+129T>C		intron_variant		3		ENSP00000370240.1
AKR1C1	ENST00000477661.1	n.690T>C		non_coding_transcript_exon_variant	3/8	5

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104966 AN: 151970 Hom.: 36469 Cov.: 33

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.706

GnomAD4 exome AF: 0.671 AC: 634581 AN: 945078 Hom.: 214762 Cov.: 12 AF XY: 0.670 AC XY: 321156 AN XY: 479358

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.817

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.673

GnomAD4 genome AF: 0.691 AC: 105044 AN: 152086 Hom.: 36500 Cov.: 33 AF XY: 0.695 AC XY: 51641 AN XY: 74330

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.710

Alfa AF: 0.664 Hom.: 55517

Bravo AF: 0.694

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.61

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: rs2904802; hg19: chr10-5009364;