NM_001818.5:c.370-622G>A

Variant names:

• chr10-5205135-G-A
• rs17134533
• NM_001818.5:c.370-622G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001818.5(AKR1C4):​c.370-622G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,200 control chromosomes in the GnomAD database, including 1,187 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 (1187 hom., cov: 33)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 7 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=-1.07).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5	c.370-622G>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.370-622G>A		intron_variant	Intron 3 of 8	1	NM_001818.5	ENSP00000263126.1
AKR1C4	ENST00000380448.5	c.370-622G>A		intron_variant	Intron 5 of 10	5		ENSP00000369814.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17181 AN: 152082 Hom.: 1184 Cov.: 33

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.113 AC: 17197 AN: 152200 Hom.: 1187 Cov.: 33 AF XY: 0.113 AC XY: 8406 AN XY: 74386

African (AFR) AF: 0.0384 AC: 1595 AN: 41542

American (AMR) AF: 0.167 AC: 2549 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3470

East Asian (EAS) AF: 0.102 AC: 530 AN: 5182

South Asian (SAS) AF: 0.107 AC: 517 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1301 AN: 10574

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

European-Non Finnish (NFE) AF: 0.147 AC: 10018 AN: 68008

Other (OTH) AF: 0.101 AC: 213 AN: 2108

Alfa AF: 0.0851 Hom.: 128

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	-1.1
CADD	Benign	0.33
DANN	Benign	0.42
PhyloP100		-2.2
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: rs17134533; hg19: chr10-5247098;