NM_001353.6:c.571-250G>C

Variant names:

• chr10-4971951-G-C
• rs3930965
• NM_001353.6:c.571-250G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001353.6(AKR1C1):​c.571-250G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 135,690 control chromosomes in the GnomAD database, including 7,163 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 0.32 (7163 hom., cov: 25)
• Consequence: AKR1C1 NM_001353.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• 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]

LOC124902365 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BS2: High Homozygotes in GnomAd4 at 7163 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C1	NM_001353.6	c.571-250G>C		intron_variant	Intron 5 of 8	ENST00000380872.9	NP_001344.2
LOC124902365	XR_007062038.1	n.342C>G		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C1	ENST00000380872.9	c.571-250G>C		intron_variant	Intron 5 of 8	1	NM_001353.6	ENSP00000370254.4
AKR1C1	ENST00000442997.5	c.469-250G>C		intron_variant	Intron 5 of 6	3		ENSP00000416415.1
AKR1C1	ENST00000477661.1	n.2028-250G>C		intron_variant	Intron 4 of 7	5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 43200 AN: 135582 Hom.: 7150 Cov.: 25

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0836

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.235

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.319 AC: 43251 AN: 135690 Hom.: 7163 Cov.: 25 AF XY: 0.315 AC XY: 20641 AN XY: 65618

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.446 AC: 16298 AN: 36580

American (AMR) AF: 0.249 AC: 3339 AN: 13416

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 749 AN: 3222

East Asian (EAS) AF: 0.0834 AC: 374 AN: 4486

South Asian (SAS) AF: 0.303 AC: 1202 AN: 3962

European-Finnish (FIN) AF: 0.331 AC: 2977 AN: 8996

Middle Eastern (MID) AF: 0.230 AC: 63 AN: 274

European-Non Finnish (NFE) AF: 0.282 AC: 17527 AN: 62096

Other (OTH) AF: 0.288 AC: 521 AN: 1810

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.135 Hom.: 208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.52
PhyloP100		-2.1
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: rs3930965; hg19: chr10-5014143;