rs11253042

Variant names:

• chr10-5204621-C-A
• rs11253042
• NM_001818.5:c.369+128C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-5204621-C-A
• chr10-5204621-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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 (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5	c.369+128C>A		intron_variant	Intron 3 of 8	ENST00000263126.3	NP_001809.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3	c.369+128C>A		intron_variant	Intron 3 of 8	1	NM_001818.5	ENSP00000263126.1
AKR1C4	ENST00000380448.5	c.369+128C>A		intron_variant	Intron 5 of 10	5		ENSP00000369814.1

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

GnomAD2 exomes AF: 0.398 AC: 96219 AN: 241508 AF XY: 0.406

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 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

African (AFR) AF: 0.171 AC: 3107 AN: 18174

American (AMR) AF: 0.282 AC: 12235 AN: 43370

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 8464 AN: 21112

East Asian (EAS) AF: 0.271 AC: 9750 AN: 35982

South Asian (SAS) AF: 0.323 AC: 22445 AN: 69440

European-Finnish (FIN) AF: 0.552 AC: 24928 AN: 45178

Middle Eastern (MID) AF: 0.440 AC: 1847 AN: 4198

European-Non Finnish (NFE) AF: 0.495 AC: 188948 AN: 381854

Other (OTH) AF: 0.441 AC: 15027 AN: 34088

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

African (AFR) AF: 0.179 AC: 7432 AN: 41496

American (AMR) AF: 0.382 AC: 5845 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1345 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1353 AN: 5152

South Asian (SAS) AF: 0.311 AC: 1496 AN: 4814

European-Finnish (FIN) AF: 0.574 AC: 6049 AN: 10540

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33563 AN: 67956

Other (OTH) AF: 0.423 AC: 893 AN: 2110

Alfa AF: 0.452 Hom.: 24075

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
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11253042; hg19: chr10-5246584; COSMIC: COSV54123322; COSMIC: COSV54123322;