chr1-209687323-T-C

Position:

• chr1-209687323-T-C

Variant summary

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

The NR_134510.1(HSD11B1-AS1):​n.67-24262A>G 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 0.771 in 152,094 control chromosomes in the GnomAD database, including 46,530 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 0.77 (46530 hom., cov: 32)
• Consequence: HSD11B1-AS1 NR_134510.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B1-AS1	NR_134510.1	n.67-24262A>G		intron_variant, non_coding_transcript_variant
HSD11B1	NM_001206741.2	c.-49+1038T>C		intron_variant
HSD11B1	NM_181755.3	c.-27+1038T>C		intron_variant
HSD11B1-AS1	NR_134509.1	n.97-24262A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B1-AS1	ENST00000441672.1	n.97-24262A>G		intron_variant, non_coding_transcript_variant		3
HSD11B1	ENST00000261465.5	c.-49+1038T>C		intron_variant		5
HSD11B1	ENST00000367028.6	c.-49+1038T>C		intron_variant		5		P1
HSD11B1	ENST00000615289.4	c.-27+1038T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117232 AN: 151976 Hom.: 46510 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.771 AC: 117296 AN: 152094 Hom.: 46530 Cov.: 32 AF XY: 0.773 AC XY: 57486 AN XY: 74366

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.915

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.811

Alfa AF: 0.837 Hom.: 34024

Bravo AF: 0.758

Asia WGS AF: 0.684 AC: 2377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2235543; hg19: chr1-209860668;