rs10904440

Variant names:

• chr10-5207807-G-A
• rs10904440
• NM_001818.5:c.570+1410G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001818.5(AKR1C4):​c.570+1410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 347,332 control chromosomes in the GnomAD database, including 129,716 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 0.79 (50350 hom., cov: 33)
  • Exomes 𝑓: 0.90 (79366 hom.)
• Consequence: AKR1C4 NM_001818.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 1 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]

ARL4AP3 (HGNC:52372): (ADP ribosylation factor like GTPase 4A pseudogene 3)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C4	NM_001818.5	MANE Select	c.570+1410G>A		intron	N/A	NP_001809.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C4	ENST00000263126.3	TSL:1 MANE Select	c.570+1410G>A		intron	N/A	ENSP00000263126.1
	AKR1C4	ENST00000380448.5	TSL:5	c.570+1410G>A		intron	N/A	ENSP00000369814.1
	ARL4AP3	ENST00000441452.1	TSL:6	n.*65G>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120639 AN: 152072 Hom.: 50330 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.813

GnomAD4 exome AF: 0.900 AC: 175558 AN: 195142 Hom.: 79366 AF XY: 0.901 AC XY: 98399 AN XY: 109262

African (AFR) AF: 0.498 AC: 1893 AN: 3802

American (AMR) AF: 0.911 AC: 7367 AN: 8084

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 3614 AN: 4192

East Asian (EAS) AF: 0.979 AC: 6181 AN: 6312

South Asian (SAS) AF: 0.903 AC: 32845 AN: 36368

European-Finnish (FIN) AF: 0.933 AC: 16398 AN: 17576

Middle Eastern (MID) AF: 0.831 AC: 550 AN: 662

European-Non Finnish (NFE) AF: 0.905 AC: 98628 AN: 109038

Other (OTH) AF: 0.887 AC: 8082 AN: 9108

GnomAD4 genome AF: 0.793 AC: 120703 AN: 152190 Hom.: 50350 Cov.: 33 AF XY: 0.800 AC XY: 59563 AN XY: 74418

African (AFR) AF: 0.503 AC: 20864 AN: 41450

American (AMR) AF: 0.882 AC: 13478 AN: 15286

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

East Asian (EAS) AF: 0.978 AC: 5073 AN: 5186

South Asian (SAS) AF: 0.902 AC: 4357 AN: 4832

European-Finnish (FIN) AF: 0.933 AC: 9911 AN: 10618

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61256 AN: 68028

Other (OTH) AF: 0.814 AC: 1719 AN: 2112

Alfa AF: 0.837 Hom.: 6827

Bravo AF: 0.779

Asia WGS AF: 0.898 AC: 3123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		-0.72
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: rs10904440; hg19: chr10-5249770;