Variant chr16-67430908-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000567261.1(ENSG00000261320):n.234C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,026 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.026 ( 51 hom., cov: 32)

Exomes 𝑓: 0.020 ( 1 hom. )

Consequence

ENST00000567261.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.502

Variant links:

Genes affected

(HGNC:):

links:

HSD11B2 (HGNC:5209): (hydroxysteroid 11-beta dehydrogenase 2) There are at least two isozymes of the corticosteroid 11-beta-dehydrogenase, a microsomal enzyme complex responsible for the interconversion of cortisol and cortisone. The type I isozyme has both 11-beta-dehydrogenase (cortisol to cortisone) and 11-oxoreductase (cortisone to cortisol) activities. The type II isozyme, encoded by this gene, has only 11-beta-dehydrogenase activity. In aldosterone-selective epithelial tissues such as the kidney, the type II isozyme catalyzes the glucocorticoid cortisol to the inactive metabolite cortisone, thus preventing illicit activation of the mineralocorticoid receptor. In tissues that do not express the mineralocorticoid receptor, such as the placenta and testis, it protects cells from the growth-inhibiting and/or pro-apoptotic effects of cortisol, particularly during embryonic development. Mutations in this gene cause the syndrome of apparent mineralocorticoid excess and hypertension. [provided by RefSeq, Feb 2010]

HSD11B2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 16-67430908-G-A is Benign according to our data. Variant chr16-67430908-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1208628.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0259 (3869/149426) while in subpopulation NFE AF= 0.031 (2081/67200). AF 95% confidence interval is 0.0299. There are 51 homozygotes in gnomad4. There are 1813 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD11B2	XM_047434048.1 linkuse as main transcript	c.-48+129G>A		intron_variant			XP_047290004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000567261.1 linkuse as main transcript	n.234C>T		non_coding_transcript_exon_variant	2/2	3
HSD11B2	ENST00000567684.2 linkuse as main transcript	n.128+129G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3863

AN:

149336

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.0312

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00828

Gnomad SAS

AF:

0.0291

Gnomad FIN

AF:

0.00951

Gnomad MID

AF:

0.0390

Gnomad NFE

AF:

0.0309

Gnomad OTH

AF:

0.0300

GnomAD4 exome

AF:

0.0204

AC:

AN:

2600

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

AN XY:

1392

show subpopulations

Gnomad4 AFR exome

AF:

0.0326

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0256

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00532

Gnomad4 NFE exome

AF:

0.0237

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0259

AC:

3869

AN:

149426

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

1813

AN XY:

72858

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00851

Gnomad4 SAS

AF:

0.0289

Gnomad4 FIN

AF:

0.00951

Gnomad4 NFE

AF:

0.0310

Gnomad4 OTH

AF:

0.0321

Alfa

AF:

0.0294

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.0290

AC:

AN:

3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2019

This variant is associated with the following publications: (PMID: 17551100) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.8

DANN

Benign

0.92

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over