rs11253048

Variant names:

• chr10-5219196-A-G
• rs11253048
• NM_001818.5:c.*436A>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.*436A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,134 control chromosomes in the GnomAD database, including 1,925 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 0.16 (1925 hom., cov: 32)
• Consequence: AKR1C4 NM_001818.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5	c.*436A>G		downstream_gene_variant		ENST00000263126.3	NP_001809.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3	c.*436A>G		downstream_gene_variant		1	NM_001818.5	ENSP00000263126.1
AKR1C4	ENST00000380448.5	c.*436A>G		downstream_gene_variant		5		ENSP00000369814.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23818 AN: 152016 Hom.: 1921 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.157 AC: 23855 AN: 152134 Hom.: 1925 Cov.: 32 AF XY: 0.155 AC XY: 11525 AN XY: 74388

African (AFR) AF: 0.136 AC: 5636 AN: 41516

American (AMR) AF: 0.198 AC: 3026 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3468

East Asian (EAS) AF: 0.102 AC: 527 AN: 5170

South Asian (SAS) AF: 0.126 AC: 606 AN: 4820

European-Finnish (FIN) AF: 0.137 AC: 1447 AN: 10584

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11598 AN: 67982

Other (OTH) AF: 0.148 AC: 312 AN: 2114

Alfa AF: 0.167 Hom.: 3264

Bravo AF: 0.162

Asia WGS AF: 0.106 AC: 369 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	1.7
DANN	Benign	0.42
PhyloP100		-0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11253048; hg19: chr10-5261159;