rs10904440

chr10-5207807-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001818.5(AKR1C4):c.570+1410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 347,332 control chromosomes in the GnomAD database, including 129,716 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 0.79 (50350 hom., cov: 33)
  • Exomes 𝑓: 0.90 (79366 hom.)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C4	NM_001818.5	c.570+1410G>A		intron_variant		ENST00000263126.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C4	ENST00000263126.3	c.570+1410G>A		intron_variant		1	NM_001818.5	P1
AKR1C4	ENST00000380448.5	c.570+1410G>A		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120639 AN: 152072 Hom.: 50330 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.813

GnomAD4 exome AF: 0.900 AC: 175558 AN: 195142 Hom.: 79366 AF XY: 0.901 AC XY: 98399 AN XY: 109262

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.911

Gnomad4 ASJ exome AF: 0.862

Gnomad4 EAS exome AF: 0.979

Gnomad4 SAS exome AF: 0.903

Gnomad4 FIN exome AF: 0.933

Gnomad4 NFE exome AF: 0.905

Gnomad4 OTH exome AF: 0.887

GnomAD4 genome AF: 0.793 AC: 120703 AN: 152190 Hom.: 50350 Cov.: 33 AF XY: 0.800 AC XY: 59563 AN XY: 74418

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.814

Alfa AF: 0.837 Hom.: 6827

Bravo AF: 0.779

Asia WGS AF: 0.898 AC: 3123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	12
Dann	Benign	0.69

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: rs10904440; hg19: chr10-5249770;