10-4991645-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001393392.1(AKR1C2):c.929+186G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3050 hom., cov: 20)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.756

Genes affected

AKR1C2 (HGNC:385): (aldo-keto reductase family 1 member C2) 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 using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme binds bile acid with high affinity, and shows minimal 3-alpha-hydroxysteroid dehydrogenase activity. 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 two different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-4991645-C-A is Benign according to our data. Variant chr10-4991645-C-A is described in ClinVar as [Benign]. Clinvar id is 1283504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1	c.929+186G>T		intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9	c.929+186G>T		intron_variant		1	NM_001393392.1	P1
AKR1C2	ENST00000421196.7	c.851+186G>T		intron_variant		1
AKR1C2	ENST00000460124.5	n.2389+186G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.204 AC: 29758 AN: 145548 Hom.: 3055 Cov.: 20

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.204 AC: 29765 AN: 145642 Hom.: 3050 Cov.: 20 AF XY: 0.200 AC XY: 14124 AN XY: 70638

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.220

Alfa AF: 0.208 Hom.: 336

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.39
Dann	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201759252; hg19: chr10-5033837; COSMIC: COSV66333113; COSMIC: COSV66333113;