NM_003739.6:c.447+66A>G

Variant names:

• chr10-5098945-A-G
• rs10508293
• NM_003739.6:c.447+66A>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.447+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,301,388 control chromosomes in the GnomAD database, including 39,366 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 0.20 (4063 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35303 hom.)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 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.447+66A>G		intron	N/A	NP_003730.4
	AKR1C3	NM_001253908.2		c.447+66A>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.447+66A>G		intron	N/A	ENSP00000369927.3	P42330-1
	AKR1C3	ENST00000605322.1	TSL:1	n.280-382A>G		intron	N/A
	AKR1C3	ENST00000439082.7	TSL:5	c.447+66A>G		intron	N/A	ENSP00000401327.3	A0A0A0MSS8

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30170 AN: 152054 Hom.: 4065 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.213 AC: 244905 AN: 1149216 Hom.: 35303 AF XY: 0.219 AC XY: 127563 AN XY: 581540

African (AFR) AF: 0.137 AC: 3529 AN: 25666

American (AMR) AF: 0.416 AC: 13602 AN: 32668

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 7546 AN: 22634

East Asian (EAS) AF: 0.713 AC: 27072 AN: 37960

South Asian (SAS) AF: 0.435 AC: 31595 AN: 72598

European-Finnish (FIN) AF: 0.111 AC: 5780 AN: 52150

Middle Eastern (MID) AF: 0.259 AC: 1328 AN: 5120

European-Non Finnish (NFE) AF: 0.168 AC: 143295 AN: 850520

Other (OTH) AF: 0.224 AC: 11158 AN: 49900

GnomAD4 genome AF: 0.198 AC: 30174 AN: 152172 Hom.: 4063 Cov.: 32 AF XY: 0.205 AC XY: 15214 AN XY: 74380

African (AFR) AF: 0.136 AC: 5666 AN: 41526

American (AMR) AF: 0.299 AC: 4565 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1163 AN: 3466

East Asian (EAS) AF: 0.657 AC: 3392 AN: 5164

South Asian (SAS) AF: 0.452 AC: 2177 AN: 4812

European-Finnish (FIN) AF: 0.108 AC: 1148 AN: 10600

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11380 AN: 68000

Other (OTH) AF: 0.227 AC: 479 AN: 2108

Alfa AF: 0.190 Hom.: 1651

Bravo AF: 0.210

Asia WGS AF: 0.512 AC: 1781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.45
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10508293; hg19: chr10-5141137;