10-5104377-A-G

Variant names:

• chr10-5104377-A-G
• rs11252946
• NM_003739.6:c.847-1218A>G

Variant summary

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

The NM_003739.6(AKR1C3):​c.847-1218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 105,004 control chromosomes in the GnomAD database, including 5,395 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 0.38 (5395 hom., cov: 32)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 1 publications found

Genes affected

AKR1C3 (HGNC:386): (aldo-keto reductase family 1 member C3) 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 reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003739.6. 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
	AKR1C3	NM_003739.6	MANE Select	c.847-1218A>G		intron	N/A	NP_003730.4
	AKR1C3	NM_001253908.2		c.847-1218A>G		intron	N/A	NP_001240837.1	A0A0A0MSS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C3	ENST00000380554.5	TSL:1 MANE Select	c.847-1218A>G		intron	N/A	ENSP00000369927.3	P42330-1
	AKR1C3	ENST00000439082.7	TSL:5	c.847-1218A>G		intron	N/A	ENSP00000401327.3	A0A0A0MSS8
	AKR1C3	ENST00000879767.1		c.847-1218A>G		intron	N/A	ENSP00000549826.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 39595 AN: 104920 Hom.: 5381 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.479

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.378 AC: 39640 AN: 105004 Hom.: 5395 Cov.: 32 AF XY: 0.375 AC XY: 19098 AN XY: 50954

African (AFR) AF: 0.493 AC: 13357 AN: 27118

American (AMR) AF: 0.345 AC: 3606 AN: 10464

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 914 AN: 2368

East Asian (EAS) AF: 0.357 AC: 1195 AN: 3348

South Asian (SAS) AF: 0.354 AC: 1030 AN: 2908

European-Finnish (FIN) AF: 0.334 AC: 2356 AN: 7050

Middle Eastern (MID) AF: 0.482 AC: 106 AN: 220

European-Non Finnish (NFE) AF: 0.326 AC: 16110 AN: 49348

Other (OTH) AF: 0.449 AC: 652 AN: 1452

Alfa AF: 0.254 Hom.: 662

Bravo AF: 0.267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.76
DANN	Benign	0.42
PhyloP100		-0.27
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: rs11252946; hg19: chr10-5146569;