rs1832007

Variant names:

• chr10-5212884-A-G
• rs1832007
• NM_001818.5:c.681-110A>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.681-110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,449,722 control chromosomes in the GnomAD database, including 15,245 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 0.11 (1185 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14060 hom.)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 50 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5	c.681-110A>G		intron_variant	Intron 6 of 8	ENST00000263126.3	NP_001809.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3	c.681-110A>G		intron_variant	Intron 6 of 8	1	NM_001818.5	ENSP00000263126.1
AKR1C4	ENST00000380448.5	c.681-110A>G		intron_variant	Intron 8 of 10	5		ENSP00000369814.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17158 AN: 152022 Hom.: 1182 Cov.: 32

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.143 AC: 185991 AN: 1297582 Hom.: 14060 Cov.: 22 AF XY: 0.142 AC XY: 90244 AN XY: 637490

African (AFR) AF: 0.0322 AC: 956 AN: 29660

American (AMR) AF: 0.204 AC: 6439 AN: 31578

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 2045 AN: 20968

East Asian (EAS) AF: 0.0907 AC: 3323 AN: 36656

South Asian (SAS) AF: 0.104 AC: 7286 AN: 69764

European-Finnish (FIN) AF: 0.134 AC: 6477 AN: 48246

Middle Eastern (MID) AF: 0.0710 AC: 379 AN: 5336

European-Non Finnish (NFE) AF: 0.152 AC: 151907 AN: 1001230

Other (OTH) AF: 0.133 AC: 7179 AN: 54144

GnomAD4 genome AF: 0.113 AC: 17174 AN: 152140 Hom.: 1185 Cov.: 32 AF XY: 0.113 AC XY: 8401 AN XY: 74380

African (AFR) AF: 0.0382 AC: 1587 AN: 41524

American (AMR) AF: 0.167 AC: 2551 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3468

East Asian (EAS) AF: 0.102 AC: 530 AN: 5178

South Asian (SAS) AF: 0.106 AC: 512 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1306 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10002 AN: 67992

Other (OTH) AF: 0.101 AC: 212 AN: 2106

Alfa AF: 0.136 Hom.: 3926

Bravo AF: 0.114

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.48
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1832007; hg19: chr10-5254847; COSMIC: COSV54122541;