10-4995242-TC-T

Position:

• chr10-4995242-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001393392.1(AKR1C2):​c.846+76del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (196 hom., cov: 17)
  • Exomes 𝑓: 0.068 (1355 hom.)
  • Failed GnomAD Quality Control
• Consequence: AKR1C2 NM_001393392.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.199

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 -10 ACMG points.

• BP6: Variant 10-4995242-TC-T is Benign according to our data. Variant chr10-4995242-TC-T is described in ClinVar as [Benign]. Clinvar id is 1247763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C2	NM_001393392.1	c.846+76del		intron_variant		ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C2	ENST00000380753.9	c.846+76del		intron_variant		1	NM_001393392.1	ENSP00000370129	P1
AKR1C2	ENST00000421196.7	c.768+76del		intron_variant		1		ENSP00000392694
AKR1C2	ENST00000460124.5	n.2306+76del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 7246 AN: 133248 Hom.: 197 Cov.: 17

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.0514

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.0651

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0681 AC: 76738 AN: 1127226 Hom.: 1355 AF XY: 0.0674 AC XY: 37264 AN XY: 552724

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.0473

Gnomad4 ASJ exome AF: 0.0955

Gnomad4 EAS exome AF: 0.000121

Gnomad4 SAS exome AF: 0.0334

Gnomad4 FIN exome AF: 0.0481

Gnomad4 NFE exome AF: 0.0753

Gnomad4 OTH exome AF: 0.0668

GnomAD4 genome AF: 0.0543 AC: 7242 AN: 133358 Hom.: 196 Cov.: 17 AF XY: 0.0519 AC XY: 3319 AN XY: 63912

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.0543

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.0735

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0583 Hom.: 26

Bravo AF: 0.0534

Asia WGS AF: 0.0160 AC: 60 AN: 3462

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

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: rs200291679; hg19: chr10-5037434;