10-5212183-A-G

Position:

• chr10-5212183-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AKR1C4	NM_001818.5	c.571-433A>G		intron_variant		ENST00000263126.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C4	ENST00000263126.3	c.571-433A>G		intron_variant		1	NM_001818.5	P1
AKR1C4	ENST00000380448.5	c.571-433A>G		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.0382

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.101

Alfa AF: 0.137 Hom.: 720

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6601927; hg19: chr10-5254146;