rs860185

chr1-209704225-T-A

Variant summary

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

The NR_134510.1(HSD11B1-AS1):n.66+38272A>T 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 0.0782 in 152,254 control chromosomes in the GnomAD database, including 1,446 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 0.078 (1446 hom., cov: 32)
• Consequence: HSD11B1-AS1 NR_134510.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B1-AS1	NR_134510.1	n.66+38272A>T		intron_variant, non_coding_transcript_variant
HSD11B1	NM_001206741.2	c.-48-670T>A		intron_variant
HSD11B1	NM_181755.3	c.-26-692T>A		intron_variant
HSD11B1-AS1	NR_134509.1	n.96+19805A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B1-AS1	ENST00000441672.1	n.96+19805A>T		intron_variant, non_coding_transcript_variant		3
HSD11B1	ENST00000261465.5	c.-48-670T>A		intron_variant		5
HSD11B1	ENST00000367028.6	c.-48-670T>A		intron_variant		5		P1
HSD11B1	ENST00000615289.4	c.-26-692T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11884 AN: 152136 Hom.: 1444 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.0555

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

GnomAD4 genome AF: 0.0782 AC: 11911 AN: 152254 Hom.: 1446 Cov.: 32 AF XY: 0.0761 AC XY: 5663 AN XY: 74458

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.0291

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.0691

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00250

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0457 Hom.: 91

Bravo AF: 0.0861

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	11
Dann	Benign	0.63

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: rs860185; hg19: chr1-209877570;