1-209701909-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_134510.1(HSD11B1-AS1):n.67-38848T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,148 control chromosomes in the GnomAD database, including 67,909 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.94 (67909 hom., cov: 31)
• Consequence: HSD11B1-AS1 NR_134510.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.855

Genes affected

HSD11B1-AS1 (HGNC:54053): (HSD11B1 antisense RNA 1)

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B1-AS1	NR_134510.1	n.67-38848T>C		intron_variant, non_coding_transcript_variant
HSD11B1	NM_001206741.2	c.-48-2986A>G		intron_variant
HSD11B1	NM_181755.3	c.-26-3008A>G		intron_variant
HSD11B1-AS1	NR_134509.1	n.96+22121T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B1-AS1	ENST00000441672.1	n.96+22121T>C		intron_variant, non_coding_transcript_variant		3
HSD11B1	ENST00000261465.5	c.-48-2986A>G		intron_variant		5
HSD11B1	ENST00000367028.6	c.-48-2986A>G		intron_variant		5		P1
HSD11B1	ENST00000615289.4	c.-26-3008A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143390 AN: 152030 Hom.: 67847 Cov.: 31

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.943 AC: 143510 AN: 152148 Hom.: 67909 Cov.: 31 AF XY: 0.940 AC XY: 69909 AN XY: 74376

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.905

Gnomad4 FIN AF: 0.935

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.951

Alfa AF: 0.951 Hom.: 9962

Bravo AF: 0.943

Asia WGS AF: 0.841 AC: 2927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	4.3
Dann	Benign	0.84

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: rs846910; hg19: chr1-209875254;