rs1554502725

Variant names:

• chr8-38145233-TGCTGAGTAGCCACGTAA-T
• rs1554502725
• NM_000349.3:c.716_732delTTACGTGGCTACTCAGC

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_000349.3(STAR):​c.716_732delTTACGTGGCTACTCAGC​(p.Leu239HisfsTer38) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L239L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAR NM_000349.3 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.61
• Publications: 0 publications found

Genes affected

STAR (HGNC:11359): (steroidogenic acute regulatory protein) The protein encoded by this gene plays a key role in the acute regulation of steroid hormone synthesis by enhancing the conversion of cholesterol into pregnenolone. This protein permits the cleavage of cholesterol into pregnenolone by mediating the transport of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane. Mutations in this gene are a cause of congenital lipoid adrenal hyperplasia (CLAH), also called lipoid CAH. A pseudogene of this gene is located on chromosome 13. [provided by RefSeq, Jul 2008]

STAR Gene-Disease associations (from GenCC):

• congenital lipoid adrenal hyperplasia due to STAR deficency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.
• PP5: Variant 8-38145233-TGCTGAGTAGCCACGTAA-T is Pathogenic according to our data. Variant chr8-38145233-TGCTGAGTAGCCACGTAA-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 554730.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000349.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAR	NM_000349.3	MANE Select	c.716_732delTTACGTGGCTACTCAGC	p.Leu239HisfsTer38	frameshift	Exon 6 of 7	NP_000340.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAR	ENST00000276449.9	TSL:1 MANE Select	c.716_732delTTACGTGGCTACTCAGC	p.Leu239HisfsTer38	frameshift	Exon 6 of 7	ENSP00000276449.3
	STAR	ENST00000520114.1	TSL:2	n.1850_1866delTTACGTGGCTACTCAGC		non_coding_transcript_exon	Exon 4 of 4
	STAR	ENST00000522050.1	TSL:5	c.584+713_584+729delTTACGTGGCTACTCAGC		intron	N/A	ENSP00000429009.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital lipoid adrenal hyperplasia due to STAR deficency Pathogenic:1

Nov 02, 2017

Counsyl

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1554502725; hg19: chr8-38002751;