rs7083869

Variant names:

• chr10-5202332-G-A
• rs7083869
• NM_001818.5:c.252+1984G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-5202332-G-A
• chr10-5202332-G-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.252+1984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 308,008 control chromosomes in the GnomAD database, including 6,699 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 0.20 (3076 hom., cov: 33)
  • Exomes 𝑓: 0.21 (3623 hom.)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 8 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001818.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C4	NM_001818.5	MANE Select	c.252+1984G>A		intron	N/A	NP_001809.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C4	ENST00000263126.3	TSL:1 MANE Select	c.252+1984G>A		intron	N/A	ENSP00000263126.1	P17516
	AKR1C4	ENST00000901611.1		c.252+1984G>A		intron	N/A	ENSP00000571670.1
	AKR1C4	ENST00000380448.5	TSL:5	c.252+1984G>A		intron	N/A	ENSP00000369814.1	P17516

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30325 AN: 151930 Hom.: 3074 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.208 AC: 32461 AN: 155960 Hom.: 3623 AF XY: 0.207 AC XY: 18456 AN XY: 89304

African (AFR) AF: 0.236 AC: 1136 AN: 4810

American (AMR) AF: 0.172 AC: 1880 AN: 10950

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 975 AN: 4556

East Asian (EAS) AF: 0.262 AC: 1797 AN: 6864

South Asian (SAS) AF: 0.198 AC: 5635 AN: 28494

European-Finnish (FIN) AF: 0.220 AC: 1433 AN: 6520

Middle Eastern (MID) AF: 0.307 AC: 530 AN: 1726

European-Non Finnish (NFE) AF: 0.205 AC: 17363 AN: 84522

Other (OTH) AF: 0.228 AC: 1712 AN: 7518

GnomAD4 genome AF: 0.200 AC: 30343 AN: 152048 Hom.: 3076 Cov.: 33 AF XY: 0.199 AC XY: 14772 AN XY: 74336

African (AFR) AF: 0.222 AC: 9187 AN: 41452

American (AMR) AF: 0.182 AC: 2785 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1277 AN: 5172

South Asian (SAS) AF: 0.177 AC: 852 AN: 4826

European-Finnish (FIN) AF: 0.200 AC: 2118 AN: 10568

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12634 AN: 67966

Other (OTH) AF: 0.224 AC: 473 AN: 2112

Alfa AF: 0.191 Hom.: 5018

Bravo AF: 0.201

Asia WGS AF: 0.230 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		0.32
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: rs7083869; hg19: chr10-5244295;