1-209709656-C-T

Variant names:

• chr1-209709656-C-T
• rs2282739
• NM_005525.4:c.517+2528C>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+2528C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,978 control chromosomes in the GnomAD database, including 13,428 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 0.38 (13428 hom., cov: 32)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.517+2528C>T		intron_variant	Intron 4 of 5	ENST00000367027.5	NP_005516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5	c.517+2528C>T		intron_variant	Intron 4 of 5	1	NM_005525.4	ENSP00000355994.3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56983 AN: 151860 Hom.: 13386 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.376 AC: 57079 AN: 151978 Hom.: 13428 Cov.: 32 AF XY: 0.379 AC XY: 28124 AN XY: 74270

African (AFR) AF: 0.647 AC: 26810 AN: 41418

American (AMR) AF: 0.410 AC: 6260 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3472

East Asian (EAS) AF: 0.535 AC: 2756 AN: 5150

South Asian (SAS) AF: 0.356 AC: 1714 AN: 4820

European-Finnish (FIN) AF: 0.277 AC: 2930 AN: 10568

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

European-Non Finnish (NFE) AF: 0.219 AC: 14855 AN: 67974

Other (OTH) AF: 0.328 AC: 691 AN: 2106

Alfa AF: 0.269 Hom.: 8512

Bravo AF: 0.399

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.20
PhyloP100		-0.75
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: rs2282739; hg19: chr1-209883001;