1-209702170-T-C

Variant names:

• chr1-209702170-T-C
• rs3753519
• NM_001206741.2:c.-48-2725T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206741.2(HSD11B1):​c.-48-2725T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,186 control chromosomes in the GnomAD database, including 46,665 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 0.76 (46665 hom., cov: 34)
• Consequence: HSD11B1 NM_001206741.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 19 publications found

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:54053): (HSD11B1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_001206741.2	c.-48-2725T>C		intron_variant	Intron 1 of 6		NP_001193670.1
HSD11B1	NM_181755.3	c.-26-2747T>C		intron_variant	Intron 1 of 6		NP_861420.1
HSD11B1-AS1	NR_134509.1	n.96+21860A>G		intron_variant	Intron 1 of 2
HSD11B1-AS1	NR_134510.1	n.67-39109A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367028.6	c.-48-2725T>C		intron_variant	Intron 1 of 6	5		ENSP00000355995.1
HSD11B1	ENST00000261465.5	c.-48-2725T>C		intron_variant	Intron 1 of 6	5		ENSP00000261465.2
HSD11B1	ENST00000615289.4	c.-26-2747T>C		intron_variant	Intron 1 of 5	5		ENSP00000478430.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115982 AN: 152066 Hom.: 46656 Cov.: 34

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.762 AC: 116023 AN: 152186 Hom.: 46665 Cov.: 34 AF XY: 0.764 AC XY: 56843 AN XY: 74396

African (AFR) AF: 0.495 AC: 20556 AN: 41492

American (AMR) AF: 0.811 AC: 12407 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3223 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3358 AN: 5166

South Asian (SAS) AF: 0.735 AC: 3547 AN: 4826

European-Finnish (FIN) AF: 0.901 AC: 9560 AN: 10606

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60619 AN: 68010

Other (OTH) AF: 0.820 AC: 1732 AN: 2112

Alfa AF: 0.849 Hom.: 33248

Bravo AF: 0.749

Asia WGS AF: 0.696 AC: 2422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.58
PhyloP100		0.071
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3753519; hg19: chr1-209875515;