rs7097713

Variant names:

• chr10-4968923-G-A
• rs7097713
• NM_001353.6:c.549G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_001353.6(AKR1C1):​c.549G>A​(p.Lys183Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,614,164 control chromosomes in the GnomAD database, including 49 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 0.010 (31 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (18 hom.)
• Consequence: AKR1C1 NM_001353.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.129).
• BP7: Synonymous conserved (PhyloP=0.516 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00999 (1521/152276) while in subpopulation AFR AF = 0.0348 (1445/41566). AF 95% confidence interval is 0.0333. There are 31 homozygotes in GnomAd4. There are 710 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C1	NM_001353.6	MANE Select	c.549G>A	p.Lys183Lys	synonymous	Exon 5 of 9	NP_001344.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C1	ENST00000380872.9	TSL:1 MANE Select	c.549G>A	p.Lys183Lys	synonymous	Exon 5 of 9	ENSP00000370254.4	Q04828
	AKR1C1	ENST00000970520.1		c.549G>A	p.Lys183Lys	synonymous	Exon 5 of 9	ENSP00000640579.1
	AKR1C1	ENST00000859341.1		c.471G>A	p.Lys157Lys	synonymous	Exon 4 of 8	ENSP00000529400.1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1521 AN: 152158 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00256 AC: 645 AN: 251476 AF XY: 0.00184

Gnomad AFR exome AF: 0.0355

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00102 AC: 1496 AN: 1461888 Hom.: 18 Cov.: 32 AF XY: 0.000884 AC XY: 643 AN XY: 727248

African (AFR) AF: 0.0372 AC: 1247 AN: 33480

American (AMR) AF: 0.00168 AC: 75 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1112006

Other (OTH) AF: 0.00220 AC: 133 AN: 60396

GnomAD4 genome AF: 0.00999 AC: 1521 AN: 152276 Hom.: 31 Cov.: 32 AF XY: 0.00953 AC XY: 710 AN XY: 74466

African (AFR) AF: 0.0348 AC: 1445 AN: 41566

American (AMR) AF: 0.00360 AC: 55 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68018

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00252 Hom.: 4

Bravo AF: 0.0117

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.1
DANN	Benign	0.45
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism

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: rs7097713; hg19: chr10-5011115;