10-5162965-C-T

Variant names:

• chr10-5162965-C-T
• rs7097295
• NM_001395972.1:c.149G>A

Variant summary

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

The NM_001395972.1(AKR1C8):​c.149G>A​(p.Arg50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 534,018 control chromosomes in the GnomAD database, including 25,589 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 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 0.29 (7090 hom., cov: 32)
  • Exomes 𝑓: 0.29 (18499 hom.)
• Consequence: AKR1C8 NM_001395972.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 13 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=0.005404532).
• 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.149G>A	p.Arg50His	missense_variant	Exon 2 of 9	ENST00000648824.2	NP_001382901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C8	ENST00000648824.2	c.149G>A	p.Arg50His	missense_variant	Exon 2 of 9		NM_001395972.1	ENSP00000496804.1
AKR1C8	ENST00000650030.1	c.149G>A	p.Arg50His	missense_variant	Exon 2 of 4			ENSP00000497014.1
AKR1C8	ENST00000578467.2	n.232G>A		non_coding_transcript_exon_variant	Exon 2 of 8	2
AKR1C8	ENST00000584929.7	n.149G>A		non_coding_transcript_exon_variant	Exon 2 of 10	6		ENSP00000496857.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43977 AN: 151898 Hom.: 7088 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.253

GnomAD2 exomes AF: 0.273 AC: 68466 AN: 251150 AF XY: 0.275

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.00185

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.292 AC: 111450 AN: 382002 Hom.: 18499 Cov.: 0 AF XY: 0.287 AC XY: 62398 AN XY: 217470

African (AFR) AF: 0.217 AC: 2276 AN: 10494

American (AMR) AF: 0.158 AC: 5746 AN: 36282

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 2811 AN: 11732

East Asian (EAS) AF: 0.00182 AC: 24 AN: 13170

South Asian (SAS) AF: 0.197 AC: 13163 AN: 66670

European-Finnish (FIN) AF: 0.408 AC: 13164 AN: 32294

Middle Eastern (MID) AF: 0.151 AC: 430 AN: 2852

European-Non Finnish (NFE) AF: 0.359 AC: 68884 AN: 191804

Other (OTH) AF: 0.296 AC: 4952 AN: 16704

GnomAD4 genome AF: 0.289 AC: 44001 AN: 152016 Hom.: 7090 Cov.: 32 AF XY: 0.289 AC XY: 21437 AN XY: 74286

African (AFR) AF: 0.214 AC: 8863 AN: 41472

American (AMR) AF: 0.243 AC: 3715 AN: 15276

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

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5166

South Asian (SAS) AF: 0.183 AC: 883 AN: 4822

European-Finnish (FIN) AF: 0.403 AC: 4259 AN: 10560

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24539 AN: 67938

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.290 Hom.: 6717

Bravo AF: 0.273

TwinsUK AF: 0.358 AC: 1327

ALSPAC AF: 0.371 AC: 1431

ESP6500AA AF: 0.231 AC: 1018

ESP6500EA AF: 0.353 AC: 3040

ExAC AF: 0.274 AC: 33271

Asia WGS AF: 0.100 AC: 347 AN: 3478

EpiCase AF: 0.347

EpiControl AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.92	D;D
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-0.97	T
PhyloP100		2.1
GERP RS		1.4
Varity_R		0.047
gMVP		0.74

Splicing

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

Other links and lift over

dbSNP: rs7097295; hg19: chr10-5204928;