dbSNP rs2020172: AKR1C8:p.Cys209Phe (chr10-5158663-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001395972.1(AKR1C8):c.626G>T(p.Cys209Phe) variant causes a missense change. The variant allele was found at a frequency of 0.283 in 489,726 control chromosomes in the GnomAD database, including 22,572 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 0.28 ( 6762 hom., cov: 32)

Exomes 𝑓: 0.28 ( 15810 hom. )

Consequence

AKR1C8
NM_001395972.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.64

Variant links:

Genes affected

AKR1C8 (HGNC:23469): (aldo-keto reductase family 1 member C8) Predicted to enable D-threo-aldose 1-dehydrogenase activity; aldo-keto reductase (NADP) activity; and estradiol 17-beta-dehydrogenase activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AKR1C8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050997436).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C8	NM_001395972.1 link	c.626G>T	p.Cys209Phe	missense_variant	Exon 6 of 9	ENST00000648824.2	NP_001382901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AKR1C8	ENST00000648824.2 link	c.626G>T	p.Cys209Phe	missense_variant	Exon 6 of 9		NM_001395972.1	ENSP00000496804.1	A0A3B3IRI8
AKR1C8	ENST00000584929.7 link	n.*292G>T		non_coding_transcript_exon_variant	Exon 7 of 10	6		ENSP00000496857.1	Q5T2L2
AKR1C8	ENST00000584929.7 link	n.*292G>T		3_prime_UTR_variant	Exon 7 of 10	6		ENSP00000496857.1	Q5T2L2
AKR1C8	ENST00000578467.2 link	n.719-863G>T		intron_variant	Intron 6 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42375

AN:

151910

Hom.:

6762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.404

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.249

AC:

44693

AN:

179672

Hom.:

6937

AF XY:

0.249

AC XY:

23878

AN XY:

95868

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.404

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.285

AC:

96184

AN:

337700

Hom.:

15810

Cov.:

AF XY:

0.279

AC XY:

53118

AN XY:

190712

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.00167

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.400

Gnomad4 NFE exome

AF:

0.354

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.279

AC:

42388

AN:

152026

Hom.:

6762

Cov.:

AF XY:

0.279

AC XY:

20698

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.239

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.404

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.243

Alfa

AF:

0.324

Hom.:

3970

Bravo

AF:

0.261

TwinsUK

AF:

0.358

AC:

1329

ALSPAC

AF:

0.371

AC:

1431

ExAC

AF:

0.165

AC:

18788

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.99

GERP RS

3.7

gMVP

0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over