rs860185

Variant names:

• chr1-209704225-T-A
• rs860185
• NM_001206741.2:c.-48-670T>A

Variant summary

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

The NM_001206741.2(HSD11B1):​c.-48-670T>A variant causes a intron 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 NM_001206741.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206741.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	NM_001206741.2		c.-48-670T>A		intron	N/A	NP_001193670.1
	HSD11B1	NM_181755.3		c.-26-692T>A		intron	N/A	NP_861420.1
	HSD11B1-AS1	NR_134509.1		n.96+19805A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367028.6	TSL:5	c.-48-670T>A		intron	N/A	ENSP00000355995.1
	HSD11B1	ENST00000261465.5	TSL:5	c.-48-670T>A		intron	N/A	ENSP00000261465.2
	HSD11B1	ENST00000615289.4	TSL:5	c.-26-692T>A		intron	N/A	ENSP00000478430.1

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

African (AFR) AF: 0.257 AC: 10656 AN: 41502

American (AMR) AF: 0.0291 AC: 446 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5192

South Asian (SAS) AF: 0.0691 AC: 333 AN: 4818

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00250 AC: 170 AN: 68032

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		1.4
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: rs860185; hg19: chr1-209877570;