chr8-38146907-T-C

Variant names:

• chr8-38146907-T-C
• rs16887217
• NM_000349.3:c.307-460A>G

Variant summary

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

The NM_000349.3(STAR):​c.307-460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 151,822 control chromosomes in the GnomAD database, including 124 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 0.011 (124 hom., cov: 30)
• Consequence: STAR NM_000349.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAR	NM_000349.3	c.307-460A>G		intron_variant	Intron 3 of 6	ENST00000276449.9	NP_000340.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAR	ENST00000276449.9	c.307-460A>G		intron_variant	Intron 3 of 6	1	NM_000349.3	ENSP00000276449.3
STAR	ENST00000522050.1	c.241-460A>G		intron_variant	Intron 2 of 4	5		ENSP00000429009.1
STAR	ENST00000521236.1	c.61-460A>G		intron_variant	Intron 3 of 3	3		ENSP00000430030.1
STAR	ENST00000520114.1	n.794-460A>G		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1743 AN: 151726 Hom.: 126 Cov.: 30

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.00730

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.00909

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

GnomAD4 genome AF: 0.0114 AC: 1737 AN: 151822 Hom.: 124 Cov.: 30 AF XY: 0.0146 AC XY: 1084 AN XY: 74192

African (AFR) AF: 0.00116 AC: 48 AN: 41436

American (AMR) AF: 0.00184 AC: 28 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.151 AC: 781 AN: 5168

South Asian (SAS) AF: 0.144 AC: 692 AN: 4806

European-Finnish (FIN) AF: 0.00730 AC: 76 AN: 10418

Middle Eastern (MID) AF: 0.0105 AC: 3 AN: 286

European-Non Finnish (NFE) AF: 0.00116 AC: 79 AN: 67956

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.00477 Hom.: 67

Bravo AF: 0.00738

Asia WGS AF: 0.136 AC: 471 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.36
PhyloP100		0.12
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: rs16887217; hg19: chr8-38004425;