rs6672256

Variant names:

• chr1-209720698-T-A
• rs6672256
• NM_005525.4:c.518-11738T>A

Variant summary

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

The NM_005525.4(HSD11B1):​c.518-11738T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,672 control chromosomes in the GnomAD database, including 3,005 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 0.20 (3005 hom., cov: 31)
• Consequence: HSD11B1 NM_005525.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.518-11738T>A		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.518-11738T>A		intron_variant	Intron 4 of 5	1	NM_005525.4	ENSP00000355994.3

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29842 AN: 151554 Hom.: 2996 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.197 AC: 29883 AN: 151672 Hom.: 3005 Cov.: 31 AF XY: 0.198 AC XY: 14656 AN XY: 74080

African (AFR) AF: 0.177 AC: 7328 AN: 41346

American (AMR) AF: 0.177 AC: 2698 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1116 AN: 5152

South Asian (SAS) AF: 0.170 AC: 814 AN: 4784

European-Finnish (FIN) AF: 0.266 AC: 2797 AN: 10506

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13795 AN: 67896

Other (OTH) AF: 0.191 AC: 399 AN: 2092

Alfa AF: 0.209 Hom.: 453

Bravo AF: 0.194

Asia WGS AF: 0.210 AC: 732 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.32
PhyloP100		-1.0
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: rs6672256; hg19: chr1-209894043;