rs2020172

Variant names:

• chr10-5158663-C-A
• rs2020172
• NM_001395972.1:c.626G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-5158663-C-A
• chr10-5158663-C-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	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	Appris	UniProt
AKR1C8	ENST00000648824.2	c.626G>T	p.Cys209Phe	missense_variant	Exon 6 of 9		NM_001395972.1	ENSP00000496804.1
AKR1C8	ENST00000584929.7	n.*292G>T		non_coding_transcript_exon_variant	Exon 7 of 10	6		ENSP00000496857.1
AKR1C8	ENST00000584929.7	n.*292G>T		3_prime_UTR_variant	Exon 7 of 10	6		ENSP00000496857.1
AKR1C8	ENST00000578467.2	n.719-863G>T		intron_variant	Intron 6 of 7	2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42375 AN: 151910 Hom.: 6762 Cov.: 32

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

GnomAD2 exomes AF: 0.249 AC: 44693 AN: 179672 AF XY: 0.249

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 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.: 0 AF XY: 0.279 AC XY: 53118 AN XY: 190712

African (AFR) AF: 0.171 AC: 1589 AN: 9284

American (AMR) AF: 0.152 AC: 4706 AN: 31004

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 2626 AN: 11096

East Asian (EAS) AF: 0.00167 AC: 19 AN: 11374

South Asian (SAS) AF: 0.194 AC: 12002 AN: 61834

European-Finnish (FIN) AF: 0.400 AC: 11617 AN: 29018

Middle Eastern (MID) AF: 0.157 AC: 397 AN: 2524

European-Non Finnish (NFE) AF: 0.354 AC: 58927 AN: 166528

Other (OTH) AF: 0.286 AC: 4301 AN: 15038

GnomAD4 genome AF: 0.279 AC: 42388 AN: 152026 Hom.: 6762 Cov.: 32 AF XY: 0.279 AC XY: 20698 AN XY: 74300

African (AFR) AF: 0.176 AC: 7284 AN: 41470

American (AMR) AF: 0.242 AC: 3696 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5178

South Asian (SAS) AF: 0.183 AC: 881 AN: 4814

European-Finnish (FIN) AF: 0.404 AC: 4260 AN: 10548

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24541 AN: 67960

Other (OTH) AF: 0.243 AC: 513 AN: 2110

Alfa AF: 0.312 Hom.: 5128

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
AlphaMissense	Pathogenic	0.70
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.99	T
PhyloP100		4.6
GERP RS		3.7
gMVP		0.77

Splicing

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

Other links and lift over

dbSNP: rs2020172; hg19: chr10-5200861;