1-209710714-C-T

Variant names:

• chr1-209710714-C-T
• rs2884090
• NM_005525.4:c.517+3586C>T

Variant summary

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

The NM_005525.4(HSD11B1):​c.517+3586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,060 control chromosomes in the GnomAD database, including 15,069 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 0.39 (15069 hom., cov: 32)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005525.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	NM_005525.4	MANE Select	c.517+3586C>T		intron	N/A	NP_005516.1	X5D2L1
	HSD11B1	NM_001206741.2		c.517+3586C>T		intron	N/A	NP_001193670.1	P28845
	HSD11B1	NM_181755.3		c.517+3586C>T		intron	N/A	NP_861420.1	P28845

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD11B1	ENST00000367027.5	TSL:1 MANE Select	c.517+3586C>T		intron	N/A	ENSP00000355994.3	P28845
	HSD11B1	ENST00000367028.6	TSL:5	c.517+3586C>T		intron	N/A	ENSP00000355995.1	P28845
	HSD11B1	ENST00000966146.1		c.514+3586C>T		intron	N/A	ENSP00000636205.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59481 AN: 151940 Hom.: 15026 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.392 AC: 59578 AN: 152060 Hom.: 15069 Cov.: 32 AF XY: 0.394 AC XY: 29282 AN XY: 74306

African (AFR) AF: 0.702 AC: 29128 AN: 41470

American (AMR) AF: 0.418 AC: 6383 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3466

East Asian (EAS) AF: 0.536 AC: 2770 AN: 5164

South Asian (SAS) AF: 0.356 AC: 1717 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2935 AN: 10570

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14868 AN: 67970

Other (OTH) AF: 0.338 AC: 713 AN: 2110

Alfa AF: 0.304 Hom.: 3388

Bravo AF: 0.417

Asia WGS AF: 0.463 AC: 1607 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.22
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: rs2884090; hg19: chr1-209884059;