rs368554968

Variant names:

• chr1-209734487-C-A
• rs368554968
• NM_005525.4:c.845C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-209734487-C-A
• chr1-209734487-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005525.4(HSD11B1):​c.845C>A​(p.Thr282Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. T282M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD11B1 NM_005525.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05405751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD11B1	NM_005525.4	c.845C>A	p.Thr282Lys	missense_variant	Exon 6 of 6	ENST00000367027.5	NP_005516.1
HSD11B1	NM_001206741.2	c.845C>A	p.Thr282Lys	missense_variant	Exon 7 of 7		NP_001193670.1
HSD11B1	NM_181755.3	c.845C>A	p.Thr282Lys	missense_variant	Exon 7 of 7		NP_861420.1
HSD11B1-AS1	NR_134510.1	n.66+8010G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367027.5	c.845C>A	p.Thr282Lys	missense_variant	Exon 6 of 6	1	NM_005525.4	ENSP00000355994.3
HSD11B1	ENST00000367028.6	c.845C>A	p.Thr282Lys	missense_variant	Exon 7 of 7	5		ENSP00000355995.1
HSD11B1	ENST00000261465.5	c.*9C>A		downstream_gene_variant		5		ENSP00000261465.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0090
DANN	Benign	0.16
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.25	T;.
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.7	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.80	N;N
REVEL	Benign	0.17
Sift	Benign	0.77	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.52		Loss of sheet (P = 0.0084);Loss of sheet (P = 0.0084);
MVP		0.36
MPC		0.28
ClinPred		0.072	T
GERP RS		-9.3
Varity_R		0.14
gMVP		0.27

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: rs368554968; hg19: chr1-209907832;