rs7083869

Positions:

• chr10-5202332-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001818.5(AKR1C4):​c.252+1984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 308,008 control chromosomes in the GnomAD database, including 6,699 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 0.20 (3076 hom., cov: 33)
  • Exomes 𝑓: 0.21 (3623 hom.)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C4	NM_001818.5	c.252+1984G>A		intron_variant		ENST00000263126.3	NP_001809.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3	c.252+1984G>A		intron_variant		1	NM_001818.5	ENSP00000263126	P1
AKR1C4	ENST00000380448.5	c.252+1984G>A		intron_variant		5		ENSP00000369814	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30325 AN: 151930 Hom.: 3074 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.208 AC: 32461 AN: 155960 Hom.: 3623 AF XY: 0.207 AC XY: 18456 AN XY: 89304

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.200 AC: 30343 AN: 152048 Hom.: 3076 Cov.: 33 AF XY: 0.199 AC XY: 14772 AN XY: 74336

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.224

Alfa AF: 0.191 Hom.: 3460

Bravo AF: 0.201

Asia WGS AF: 0.230 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.92

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: rs7083869; hg19: chr10-5244295;