10-4995068-T-C

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.846+251A>G 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 0.95 (25358 hom., cov: 7)
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.112

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=-1.0).
• BP6: Variant 10-4995068-T-C is Benign according to our data. Variant chr10-4995068-T-C is described in ClinVar as [Benign]. Clinvar id is 1259007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C2	NM_001393392.1	c.846+251A>G		intron_variant		ENST00000380753.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C2	ENST00000380753.9	c.846+251A>G		intron_variant		1	NM_001393392.1	P1
AKR1C2	ENST00000421196.7	c.768+251A>G		intron_variant		1
AKR1C2	ENST00000460124.5	n.2306+251A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.953 AC: 51758 AN: 54314 Hom.: 25340 Cov.: 7

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.926

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.942

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.949

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

GnomAD4 genome AF: 0.953 AC: 51799 AN: 54376 Hom.: 25358 Cov.: 7 AF XY: 0.950 AC XY: 23435 AN XY: 24656

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.978

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.991

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.949

Alfa AF: 0.939 Hom.: 886

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

Oct 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.2
Dann	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs2801887; hg19: chr10-5037260;