chr10-5094723-A-G

Variant names:

• chr10-5094723-A-G
• rs1937843
• NM_003739.6:c.84+195A>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.84+195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,772 control chromosomes in the GnomAD database, including 8,593 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 0.33 (8593 hom., cov: 31)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6	c.84+195A>G		intron_variant	Intron 1 of 8	ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253908.2	c.85-1687A>G		intron_variant	Intron 1 of 8		NP_001240837.1
AKR1C3	NM_001253909.2	c.84+195A>G		intron_variant	Intron 1 of 2		NP_001240838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.84+195A>G		intron_variant	Intron 1 of 8	1	NM_003739.6	ENSP00000369927.3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49337 AN: 151654 Hom.: 8585 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.325 AC: 49382 AN: 151772 Hom.: 8593 Cov.: 31 AF XY: 0.324 AC XY: 23991 AN XY: 74158

African (AFR) AF: 0.336 AC: 13907 AN: 41364

American (AMR) AF: 0.256 AC: 3899 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 824 AN: 3460

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5168

South Asian (SAS) AF: 0.184 AC: 884 AN: 4810

European-Finnish (FIN) AF: 0.405 AC: 4268 AN: 10532

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24626 AN: 67888

Other (OTH) AF: 0.279 AC: 589 AN: 2108

Alfa AF: 0.339 Hom.: 3095

Bravo AF: 0.312

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.29
PhyloP100		-0.66
PromoterAI		0.10	Neutral
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: rs1937843; hg19: chr10-5136915;