10-5094307-A-G

Variant names:

• chr10-5094307-A-G
• rs3763676
• NM_001253908.2:c.85-2103A>G

Variant summary

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

The NM_001253908.2(AKR1C3):​c.85-2103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 869,958 control chromosomes in the GnomAD database, including 44,687 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 0.34 (8386 hom., cov: 23)
  • Exomes 𝑓: 0.28 (36301 hom.)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_001253908.2	c.85-2103A>G		intron_variant	Intron 1 of 8		NP_001240837.1
AKR1C3	NM_003739.6	c.-138A>G		upstream_gene_variant		ENST00000380554.5	NP_003730.4
AKR1C3	NM_001253909.2	c.-138A>G		upstream_gene_variant			NP_001240838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5	c.-138A>G		upstream_gene_variant		1	NM_003739.6	ENSP00000369927.3

Frequencies

GnomAD3 genomes AF: 0.342 AC: 48330 AN: 141336 Hom.: 8378 Cov.: 23

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.238

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.284 AC: 206544 AN: 728526 Hom.: 36301 Cov.: 10 AF XY: 0.282 AC XY: 108503 AN XY: 384344

African (AFR) AF: 0.301 AC: 5408 AN: 17986

American (AMR) AF: 0.170 AC: 5675 AN: 33410

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 3965 AN: 17878

East Asian (EAS) AF: 0.00230 AC: 62 AN: 26984

South Asian (SAS) AF: 0.194 AC: 13635 AN: 70320

European-Finnish (FIN) AF: 0.386 AC: 13626 AN: 35346

Middle Eastern (MID) AF: 0.171 AC: 466 AN: 2724

European-Non Finnish (NFE) AF: 0.315 AC: 154759 AN: 490692

Other (OTH) AF: 0.270 AC: 8948 AN: 33186

GnomAD4 genome AF: 0.342 AC: 48374 AN: 141432 Hom.: 8386 Cov.: 23 AF XY: 0.344 AC XY: 23422 AN XY: 68030

African (AFR) AF: 0.355 AC: 13549 AN: 38194

American (AMR) AF: 0.297 AC: 3803 AN: 12788

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 819 AN: 3398

East Asian (EAS) AF: 0.00368 AC: 16 AN: 4346

South Asian (SAS) AF: 0.194 AC: 841 AN: 4344

European-Finnish (FIN) AF: 0.453 AC: 4039 AN: 8918

Middle Eastern (MID) AF: 0.230 AC: 53 AN: 230

European-Non Finnish (NFE) AF: 0.367 AC: 24372 AN: 66382

Other (OTH) AF: 0.295 AC: 572 AN: 1942

Alfa AF: 0.339 Hom.: 2500

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	-0.89
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.50
PromoterAI		0.085	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3763676; hg19: chr10-5136499; COSMIC: COSV65910359; COSMIC: COSV65910359;