10-5208400-A-T

Variant names:

• chr10-5208400-A-T
• rs1413624
• NM_001818.5:c.570+2003A>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.570+2003A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 151,382 control chromosomes in the GnomAD database, including 51,619 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 0.80 (51619 hom., cov: 33)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 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.570+2003A>T		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.570+2003A>T		intron	N/A	ENSP00000263126.1	P17516
	AKR1C4	ENST00000901611.1		c.615+2003A>T		intron	N/A	ENSP00000571670.1
	AKR1C4	ENST00000380448.5	TSL:5	c.570+2003A>T		intron	N/A	ENSP00000369814.1	P17516

Frequencies

GnomAD3 genomes AF: 0.805 AC: 121704 AN: 151264 Hom.: 51596 Cov.: 33

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.804 AC: 121771 AN: 151382 Hom.: 51619 Cov.: 33 AF XY: 0.811 AC XY: 60034 AN XY: 73988

African (AFR) AF: 0.537 AC: 21879 AN: 40726

American (AMR) AF: 0.888 AC: 13551 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2968 AN: 3472

East Asian (EAS) AF: 0.978 AC: 5072 AN: 5184

South Asian (SAS) AF: 0.902 AC: 4358 AN: 4832

European-Finnish (FIN) AF: 0.934 AC: 9897 AN: 10602

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61238 AN: 67988

Other (OTH) AF: 0.818 AC: 1728 AN: 2112

Alfa AF: 0.811 Hom.: 3206

Bravo AF: 0.790

Asia WGS AF: 0.902 AC: 3129 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.0
DANN	Benign	0.29
PhyloP100		0.42
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1413624;

hg19: chr10-5250363;