chr10-4967172-T-A

Variant names:

• chr10-4967172-T-A
• rs2904802
• NM_001353.6:c.369+129T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001353.6(AKR1C1):​c.369+129T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AKR1C1 NM_001353.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C1	NM_001353.6	c.369+129T>A		intron_variant	Intron 3 of 8	ENST00000380872.9	NP_001344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C1	ENST00000380872.9	c.369+129T>A		intron_variant	Intron 3 of 8	1	NM_001353.6	ENSP00000370254.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 947204 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 480404

African (AFR) AF: 0.00 AC: 0 AN: 22100

American (AMR) AF: 0.00 AC: 0 AN: 24478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18178

East Asian (EAS) AF: 0.00 AC: 0 AN: 33734

South Asian (SAS) AF: 0.00 AC: 0 AN: 58048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4570

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 696120

Other (OTH) AF: 0.00 AC: 0 AN: 42500

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.61
PhyloP100		0.064

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

Other links and lift over

dbSNP: rs2904802; hg19: chr10-5009364;