rs11253042

chr10-5204621-C-Achr10-5204621-C-T

Variant summary

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

The NM_001818.5(AKR1C4):c.369+128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 805,418 control chromosomes in the GnomAD database, including 79,920 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 0.39 (12853 hom., cov: 32)
  • Exomes 𝑓: 0.44 (67067 hom.)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C4	NM_001818.5	c.369+128C>A		intron_variant		ENST00000263126.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C4	ENST00000263126.3	c.369+128C>A		intron_variant		1	NM_001818.5	P1
AKR1C4	ENST00000380448.5	c.369+128C>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58599 AN: 151904 Hom.: 12846 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.424

GnomAD3 exomes AF: 0.398 AC: 96219 AN: 241508 Hom.: 21116 AF XY: 0.406 AC XY: 53354 AN XY: 131308

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.251

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.569

Gnomad NFE exome AF: 0.488

Gnomad OTH exome AF: 0.452

GnomAD4 exome AF: 0.439 AC: 286751 AN: 653396 Hom.: 67067 Cov.: 8 AF XY: 0.437 AC XY: 155138 AN XY: 354662

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.386 AC: 58617 AN: 152022 Hom.: 12853 Cov.: 32 AF XY: 0.387 AC XY: 28746 AN XY: 74294

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.423

Alfa AF: 0.461 Hom.: 19175

Bravo AF: 0.363

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.18
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11253042; hg19: chr10-5246584; COSMIC: COSV54123322; COSMIC: COSV54123322;