NM_000349.3:c.179-133G>C

Variant names:

• chr8-38148460-C-G
• rs2070348
• NM_000349.3:c.179-133G>C

Variant summary

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

The NM_000349.3(STAR):​c.179-133G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,486,428 control chromosomes in the GnomAD database, including 174 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 0.0052 (23 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (151 hom.)
• Consequence: STAR NM_000349.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAR	NM_000349.3	MANE Select	c.179-133G>C		intron	N/A	NP_000340.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAR	ENST00000276449.9	TSL:1 MANE Select	c.179-133G>C		intron	N/A	ENSP00000276449.3
	STAR	ENST00000971759.1		c.179-133G>C		intron	N/A	ENSP00000641818.1
	STAR	ENST00000522050.1	TSL:5	c.113-133G>C		intron	N/A	ENSP00000429009.1

Frequencies

GnomAD3 genomes AF: 0.00523 AC: 795 AN: 152120 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.00325 AC: 4338 AN: 1334190 Hom.: 151 Cov.: 22 AF XY: 0.00314 AC XY: 2083 AN XY: 663992

African (AFR) AF: 0.000392 AC: 12 AN: 30592

American (AMR) AF: 0.0275 AC: 1006 AN: 36614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24796

East Asian (EAS) AF: 0.0805 AC: 2921 AN: 36298

South Asian (SAS) AF: 0.000493 AC: 39 AN: 79106

European-Finnish (FIN) AF: 0.000351 AC: 15 AN: 42758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4012

European-Non Finnish (NFE) AF: 0.000126 AC: 129 AN: 1023906

Other (OTH) AF: 0.00385 AC: 216 AN: 56108

GnomAD4 genome AF: 0.00522 AC: 795 AN: 152238 Hom.: 23 Cov.: 33 AF XY: 0.00601 AC XY: 447 AN XY: 74416

African (AFR) AF: 0.000794 AC: 33 AN: 41560

American (AMR) AF: 0.0267 AC: 408 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0600 AC: 310 AN: 5166

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4820

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68010

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.000200 Hom.: 0

Bravo AF: 0.00696

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.54
PhyloP100		0.15
PromoterAI		-0.0094	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2070348; hg19: chr8-38005978;