NM_001818.5:c.571-433A>G

Variant names:

• chr10-5212183-A-G
• rs6601927
• NM_001818.5:c.571-433A>G

Variant summary

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

The NM_001818.5(AKR1C4):​c.571-433A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,254 control chromosomes in the GnomAD database, including 1,183 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 0.11 (1183 hom., cov: 33)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5	c.571-433A>G		intron_variant	Intron 5 of 8	ENST00000263126.3	NP_001809.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3	c.571-433A>G		intron_variant	Intron 5 of 8	1	NM_001818.5	ENSP00000263126.1
AKR1C4	ENST00000380448.5	c.571-433A>G		intron_variant	Intron 7 of 10	5		ENSP00000369814.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17161 AN: 152136 Hom.: 1180 Cov.: 33

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.113 AC: 17177 AN: 152254 Hom.: 1183 Cov.: 33 AF XY: 0.113 AC XY: 8401 AN XY: 74456

African (AFR) AF: 0.0382 AC: 1589 AN: 41570

American (AMR) AF: 0.167 AC: 2556 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3470

East Asian (EAS) AF: 0.102 AC: 530 AN: 5188

South Asian (SAS) AF: 0.106 AC: 514 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10000 AN: 67992

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.137 Hom.: 798

Bravo AF: 0.114

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		-0.84
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: rs6601927; hg19: chr10-5254146;