1-209710714-C-T

Position:

• chr1-209710714-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD11B1	NM_005525.4	c.517+3586C>T		intron_variant		ENST00000367027.5
HSD11B1-AS1	NR_134510.1	n.66+31783G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD11B1	ENST00000367027.5	c.517+3586C>T		intron_variant		1	NM_005525.4	P1
HSD11B1-AS1	ENST00000441672.1	n.96+13316G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.338

Alfa AF: 0.304 Hom.: 2776

Bravo AF: 0.417

Asia WGS AF: 0.463 AC: 1607 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2884090; hg19: chr1-209884059;