chr16-67430991-G-A

Position:

• chr16-67430991-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000567261.1(ENSG00000261320):​n.151C>T variant causes a non coding transcript exon 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 0.026 (102 hom., cov: 31)
  • Exomes 𝑓: 0.015 (18 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENST00000567261.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.126

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-67430991-G-A is Benign according to our data. Variant chr16-67430991-G-A is described in ClinVar as [Benign]. Clinvar id is 1231382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD11B2	XM_047434048.1	c.-48+212G>A		intron_variant			XP_047290004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000567261.1	n.151C>T		non_coding_transcript_exon_variant	2/2	3
HSD11B2	ENST00000567684.2	n.128+212G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3875 AN: 151546 Hom.: 102 Cov.: 31

Gnomad AFR AF: 0.00583

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0368

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.0147 AC: 738 AN: 50156 Hom.: 18 Cov.: 0 AF XY: 0.0144 AC XY: 384 AN XY: 26686

Gnomad4 AFR exome AF: 0.00313

Gnomad4 AMR exome AF: 0.00732

Gnomad4 ASJ exome AF: 0.00781

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00826

Gnomad4 FIN exome AF: 0.0345

Gnomad4 NFE exome AF: 0.0152

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0255 AC: 3873 AN: 151652 Hom.: 102 Cov.: 31 AF XY: 0.0258 AC XY: 1913 AN XY: 74106

Gnomad4 AFR AF: 0.00581

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.0661

Gnomad4 NFE AF: 0.0368

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.00936 Hom.: 6

Bravo AF: 0.0223

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 24, 2020	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	4.6
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56057545; hg19: chr16-67464894;