10-5214222-G-C

Variant names:

• chr10-5214222-G-C
• rs12762017
• NM_001818.5:c.846+1063G>C

Variant summary

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

The NM_001818.5(AKR1C4):​c.846+1063G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,012 control chromosomes in the GnomAD database, including 1,379 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 0.12 (1379 hom., cov: 32)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 2 publications found

Genes affected

AKR1C4 (HGNC:387): (aldo-keto reductase family 1 member C4) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]

AKR1C4 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to testicular 17,20-desmolase deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5	c.846+1063G>C		intron_variant	Intron 7 of 8	ENST00000263126.3	NP_001809.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3	c.846+1063G>C		intron_variant	Intron 7 of 8	1	NM_001818.5	ENSP00000263126.1
AKR1C4	ENST00000380448.5	c.846+1063G>C		intron_variant	Intron 9 of 10	5		ENSP00000369814.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18281 AN: 151896 Hom.: 1382 Cov.: 32

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.120 AC: 18273 AN: 152012 Hom.: 1379 Cov.: 32 AF XY: 0.123 AC XY: 9148 AN XY: 74284

African (AFR) AF: 0.0335 AC: 1391 AN: 41506

American (AMR) AF: 0.134 AC: 2039 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1370 AN: 5180

South Asian (SAS) AF: 0.155 AC: 748 AN: 4812

European-Finnish (FIN) AF: 0.188 AC: 1983 AN: 10528

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9722 AN: 67940

Other (OTH) AF: 0.151 AC: 319 AN: 2112

Alfa AF: 0.0638 Hom.: 96

Bravo AF: 0.113

Asia WGS AF: 0.214 AC: 739 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.40
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12762017; hg19: chr10-5256185;