1-209734320-A-AT

Position:

• chr1-209734320-A-AT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005525.4(HSD11B1):​c.678_679insT​(p.Val227CysfsTer33) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD11B1 NM_005525.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.275

Genes affected

HSD11B1 (HGNC:5208): (hydroxysteroid 11-beta dehydrogenase 1) The protein encoded by this gene is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central obesity, and a particular variation in this gene has been associated with obesity and insulin resistance in children. Mutations in this gene and H6PD (hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)) are the cause of cortisone reductase deficiency. Alternate splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, May 2011]

HSD11B1-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B1	NM_005525.4	c.678_679insT	p.Val227CysfsTer33	frameshift_variant	6/6	ENST00000367027.5
HSD11B1-AS1	NR_134510.1	n.66+8176_66+8177insA		intron_variant, non_coding_transcript_variant
HSD11B1	NM_001206741.2	c.678_679insT	p.Val227CysfsTer33	frameshift_variant	7/7
HSD11B1	NM_181755.3	c.678_679insT	p.Val227CysfsTer33	frameshift_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B1	ENST00000367027.5	c.678_679insT	p.Val227CysfsTer33	frameshift_variant	6/6	1	NM_005525.4	P1
HSD11B1	ENST00000261465.5	c.678_679insT	p.Val227CysfsTer33	frameshift_variant	7/7	5
HSD11B1	ENST00000367028.6	c.678_679insT	p.Val227CysfsTer33	frameshift_variant	7/7	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Exstrophy-epispadias complex Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Obstetrics and Gynecology Department, Johns Hopkins School Of Medicine

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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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-209907665;