rs749071532

Variant names:

• chr1-209732526-T-A
• NM_005525.4:c.608T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-209732526-T-A
• chr1-209732526-T-C
• chr1-209732526-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005525.4(HSD11B1):​c.608T>A​(p.Val203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V203A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HSD11B1 NM_005525.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14752558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.608T>A	p.Val203Glu	missense_variant	Exon 5 of 6	ENST00000367027.5	NP_005516.1
HSD11B1	NM_001206741.2	c.608T>A	p.Val203Glu	missense_variant	Exon 6 of 7		NP_001193670.1
HSD11B1	NM_181755.3	c.608T>A	p.Val203Glu	missense_variant	Exon 6 of 7		NP_861420.1
HSD11B1-AS1	NR_134510.1	n.66+9971A>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5	c.608T>A	p.Val203Glu	missense_variant	Exon 5 of 6	1	NM_005525.4	ENSP00000355994.3
HSD11B1	ENST00000367028.6	c.608T>A	p.Val203Glu	missense_variant	Exon 6 of 7	5		ENSP00000355995.1
HSD11B1	ENST00000261465.5	c.608T>A	p.Val203Glu	missense_variant	Exon 6 of 7	5		ENSP00000261465.2
HSD11B1	ENST00000615289.4	c.*61T>A		downstream_gene_variant		5		ENSP00000478430.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461652 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Uncertain	0.77	D;.;D
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.55	T;T;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;.;L
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Benign	0.074
Sift	Uncertain	0.018	D;D;D
Sift4G	Benign	0.091	T;T;T
Polyphen		0.0040	B;.;B
Vest4		0.29
MutPred		0.41		Gain of disorder (P = 0.0037);Gain of disorder (P = 0.0037);Gain of disorder (P = 0.0037);
MVP		0.15
MPC		0.38
ClinPred		0.65	D
GERP RS		3.1
Varity_R		0.49
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-209905871;