rs41314625

Variant names:

• chr10-4968530-G-A
• rs41314625
• NM_001353.6:c.447+144G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-4968530-G-A
• chr10-4968530-G-T

Variant summary

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

The NM_001353.6(AKR1C1):​c.447+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,535,094 control chromosomes in the GnomAD database, including 12,006 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 0.094 (834 hom., cov: 31)
  • Exomes 𝑓: 0.11 (11172 hom.)
• Consequence: AKR1C1 NM_001353.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 1 publications found

Genes affected

AKR1C1 (HGNC:384): (aldo-keto reductase family 1 member C1) 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 reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353.6. 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
	AKR1C1	NM_001353.6	MANE Select	c.447+144G>A		intron	N/A	NP_001344.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C1	ENST00000380872.9	TSL:1 MANE Select	c.447+144G>A		intron	N/A	ENSP00000370254.4
	AKR1C1	ENST00000970520.1		c.447+144G>A		intron	N/A	ENSP00000640579.1
	AKR1C1	ENST00000859341.1		c.370-292G>A		intron	N/A	ENSP00000529400.1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14258 AN: 151958 Hom.: 834 Cov.: 31

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0266

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0829

GnomAD4 exome AF: 0.109 AC: 151190 AN: 1383018 Hom.: 11172 AF XY: 0.107 AC XY: 73263 AN XY: 684374

African (AFR) AF: 0.0575 AC: 1839 AN: 31976

American (AMR) AF: 0.0484 AC: 1840 AN: 38018

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 935 AN: 23548

East Asian (EAS) AF: 0.000154 AC: 6 AN: 38868

South Asian (SAS) AF: 0.0318 AC: 2508 AN: 78792

European-Finnish (FIN) AF: 0.207 AC: 10570 AN: 50946

Middle Eastern (MID) AF: 0.0513 AC: 281 AN: 5476

European-Non Finnish (NFE) AF: 0.121 AC: 127872 AN: 1057896

Other (OTH) AF: 0.0929 AC: 5339 AN: 57498

GnomAD4 genome AF: 0.0938 AC: 14262 AN: 152076 Hom.: 834 Cov.: 31 AF XY: 0.0957 AC XY: 7115 AN XY: 74334

African (AFR) AF: 0.0632 AC: 2621 AN: 41498

American (AMR) AF: 0.0620 AC: 947 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0270 AC: 130 AN: 4814

European-Finnish (FIN) AF: 0.213 AC: 2253 AN: 10562

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7974 AN: 67958

Other (OTH) AF: 0.0820 AC: 173 AN: 2110

Alfa AF: 0.0513 Hom.: 64

Bravo AF: 0.0815

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.57
DANN	Benign	0.58
PhyloP100		-1.4
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: rs41314625; hg19: chr10-5010722;