10-5119763-A-G

Variant names:

• chr10-5119763-A-G
• rs1937920
• XM_047425162.1:c.*405-2733T>C

Variant summary

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

The XM_047425162.1(AKR1C8):​c.*405-2733T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,084 control chromosomes in the GnomAD database, including 6,407 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 (6407 hom., cov: 32)
• Consequence: AKR1C8 XM_047425162.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51
• Publications: 14 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 (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C8	XM_047425162.1	c.*405-2733T>C		intron_variant	Intron 12 of 13		XP_047281118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42519 AN: 151968 Hom.: 6395 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.313

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42568 AN: 152084 Hom.: 6407 Cov.: 32 AF XY: 0.275 AC XY: 20471 AN XY: 74354

African (AFR) AF: 0.388 AC: 16103 AN: 41478

American (AMR) AF: 0.241 AC: 3681 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3468

East Asian (EAS) AF: 0.237 AC: 1227 AN: 5176

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4818

European-Finnish (FIN) AF: 0.223 AC: 2360 AN: 10578

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16107 AN: 67986

Other (OTH) AF: 0.316 AC: 666 AN: 2106

Alfa AF: 0.250 Hom.: 13500

Bravo AF: 0.288

Asia WGS AF: 0.280 AC: 974 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		2.5

Splicing

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

Other links and lift over

dbSNP: rs1937920; hg19: chr10-5161955;