rs8483

Variant names:

• chr10-4977767-G-A
• rs8483
• NM_001353.6:c.*25G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-4977767-G-A
• chr10-4977767-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353.6(AKR1C1):​c.*25G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,590,706 control chromosomes in the GnomAD database, including 132,294 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 0.47 (17510 hom., cov: 29)
  • Exomes 𝑓: 0.40 (114784 hom.)
• Consequence: AKR1C1 NM_001353.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C1	NM_001353.6	c.*25G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000380872.9	NP_001344.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C1	ENST00000380872.9	c.*25G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001353.6	ENSP00000370254.4
AKR1C1	ENST00000477661.1	n.2454G>A		non_coding_transcript_exon_variant	Exon 8 of 8	5

Frequencies

GnomAD3 genomes AF: 0.469 AC: 70998 AN: 151344 Hom.: 17475 Cov.: 29

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.460

GnomAD2 exomes AF: 0.452 AC: 110853 AN: 245420 AF XY: 0.440

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.601

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.554

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.395 AC: 568539 AN: 1439242 Hom.: 114784 Cov.: 27 AF XY: 0.393 AC XY: 282019 AN XY: 717112

African (AFR) AF: 0.611 AC: 19997 AN: 32702

American (AMR) AF: 0.591 AC: 25902 AN: 43838

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 7963 AN: 25878

East Asian (EAS) AF: 0.580 AC: 22940 AN: 39522

South Asian (SAS) AF: 0.408 AC: 34836 AN: 85458

European-Finnish (FIN) AF: 0.548 AC: 29149 AN: 53218

Middle Eastern (MID) AF: 0.331 AC: 1883 AN: 5692

European-Non Finnish (NFE) AF: 0.368 AC: 402098 AN: 1093394

Other (OTH) AF: 0.399 AC: 23771 AN: 59540

GnomAD4 genome AF: 0.469 AC: 71085 AN: 151464 Hom.: 17510 Cov.: 29 AF XY: 0.477 AC XY: 35310 AN XY: 73956

African (AFR) AF: 0.603 AC: 24886 AN: 41290

American (AMR) AF: 0.503 AC: 7660 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3466

East Asian (EAS) AF: 0.566 AC: 2896 AN: 5116

South Asian (SAS) AF: 0.413 AC: 1978 AN: 4788

European-Finnish (FIN) AF: 0.557 AC: 5829 AN: 10460

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25430 AN: 67806

Other (OTH) AF: 0.462 AC: 969 AN: 2098

Alfa AF: 0.308 Hom.: 1208

Bravo AF: 0.478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.37
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs8483; hg19: chr10-5019959; COSMIC: COSV66513764;