chr10-5101845-T-G

Variant names:

• chr10-5101845-T-G
• rs4881400
• NM_003739.6:c.571-256T>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.571-256T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,092 control chromosomes in the GnomAD database, including 5,745 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 0.26 (5745 hom., cov: 32)
• Consequence: AKR1C3 NM_003739.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 16 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 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.571-256T>G		intron	N/A	NP_003730.4
	AKR1C3	NM_001253908.2		c.571-256T>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.571-256T>G		intron	N/A	ENSP00000369927.3	P42330-1
	AKR1C3	ENST00000439082.7	TSL:5	c.571-256T>G		intron	N/A	ENSP00000401327.3	A0A0A0MSS8
	AKR1C3	ENST00000879767.1		c.571-256T>G		intron	N/A	ENSP00000549826.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38984 AN: 151976 Hom.: 5750 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.256 AC: 38990 AN: 152092 Hom.: 5745 Cov.: 32 AF XY: 0.262 AC XY: 19475 AN XY: 74360

African (AFR) AF: 0.192 AC: 7968 AN: 41502

American (AMR) AF: 0.354 AC: 5402 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3470

East Asian (EAS) AF: 0.657 AC: 3396 AN: 5168

South Asian (SAS) AF: 0.452 AC: 2178 AN: 4820

European-Finnish (FIN) AF: 0.200 AC: 2110 AN: 10574

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15698 AN: 67966

Other (OTH) AF: 0.293 AC: 619 AN: 2112

Alfa AF: 0.249 Hom.: 22838

Bravo AF: 0.267

Asia WGS AF: 0.508 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.86
PhyloP100		-0.28
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: rs4881400; hg19: chr10-5144037;