10-5202332-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001818.5(AKR1C4):​c.252+1984G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000064 in 156,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5	c.252+1984G>T		intron_variant	Intron 2 of 8	ENST00000263126.3	NP_001809.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3	c.252+1984G>T		intron_variant	Intron 2 of 8	1	NM_001818.5	ENSP00000263126.1
AKR1C4	ENST00000380448.5	c.252+1984G>T		intron_variant	Intron 4 of 10	5		ENSP00000369814.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000640 AC: 1 AN: 156170 Hom.: 0 AF XY: 0.0000112 AC XY: 1 AN XY: 89424

African (AFR) AF: 0.00 AC: 0 AN: 4814

American (AMR) AF: 0.00 AC: 0 AN: 10964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4558

East Asian (EAS) AF: 0.00 AC: 0 AN: 6866

South Asian (SAS) AF: 0.00 AC: 0 AN: 28518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1730

European-Non Finnish (NFE) AF: 0.0000118 AC: 1 AN: 84666

Other (OTH) AF: 0.00 AC: 0 AN: 7524

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.32

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;