10-5157733-C-G

Variant names:

• chr10-5157733-C-G
• rs1781935
• NM_001395972.1:c.757G>C

Variant summary

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

The NM_001395972.1(AKR1C8):​c.757G>C​(p.Gly253Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 472,110 control chromosomes in the GnomAD database, including 67,489 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (22075 hom., cov: 32)
  • Exomes 𝑓: 0.52 (45414 hom.)
• Consequence: AKR1C8 NM_001395972.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• 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 (MetaRNN=0.00946632).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395972.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C8	NM_001395972.1	MANE Select	c.757G>C	p.Gly253Arg	missense	Exon 7 of 9	NP_001382901.1
	AKR1C8	NR_027916.3		n.749G>C		non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C8	ENST00000648824.2	MANE Select	c.757G>C	p.Gly253Arg	missense	Exon 7 of 9	ENSP00000496804.1
	AKR1C8	ENST00000578467.2	TSL:2	n.786G>C		non_coding_transcript_exon	Exon 7 of 8
	AKR1C8	ENST00000584929.7	TSL:6	n.*423G>C		non_coding_transcript_exon	Exon 8 of 10	ENSP00000496857.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80005 AN: 151898 Hom.: 22065 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.516 AC: 165043 AN: 320094 Hom.: 45414 Cov.: 0 AF XY: 0.503 AC XY: 90837 AN XY: 180758

African (AFR) AF: 0.474 AC: 4089 AN: 8630

American (AMR) AF: 0.406 AC: 11061 AN: 27260

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 4439 AN: 10788

East Asian (EAS) AF: 0.137 AC: 1261 AN: 9212

South Asian (SAS) AF: 0.366 AC: 22077 AN: 60308

European-Finnish (FIN) AF: 0.662 AC: 18407 AN: 27796

Middle Eastern (MID) AF: 0.320 AC: 892 AN: 2784

European-Non Finnish (NFE) AF: 0.600 AC: 95465 AN: 158984

Other (OTH) AF: 0.513 AC: 7352 AN: 14332

GnomAD4 genome AF: 0.527 AC: 80042 AN: 152016 Hom.: 22075 Cov.: 32 AF XY: 0.526 AC XY: 39052 AN XY: 74296

African (AFR) AF: 0.468 AC: 19393 AN: 41460

American (AMR) AF: 0.492 AC: 7527 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3468

East Asian (EAS) AF: 0.141 AC: 728 AN: 5154

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4816

European-Finnish (FIN) AF: 0.670 AC: 7084 AN: 10574

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40699 AN: 67952

Other (OTH) AF: 0.464 AC: 976 AN: 2104

Alfa AF: 0.492 Hom.: 3095

Bravo AF: 0.509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.012
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0095	T
PhyloP100		-0.012
gMVP		0.36

Splicing

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

Other links and lift over

dbSNP: rs1781935; hg19: chr10-5199934;