8-38146269-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000349.3(STAR):c.465+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.985 in 1,614,026 control chromosomes in the GnomAD database, including 783,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 72617 hom., cov: 31)

Exomes 𝑓: 0.99 ( 710462 hom. )

Consequence

STAR
NM_000349.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0580

Publications

6 publications found

Variant links:

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

STAR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 8-38146269-T-C is Benign according to our data. Variant chr8-38146269-T-C is described in ClinVar as Benign. ClinVar VariationId is 448532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAR	NM_000349.3	MANE Select	c.465+20A>G		intron	N/A	NP_000340.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STAR	ENST00000276449.9	TSL:1 MANE Select	c.465+20A>G	intron	N/A	ENSP00000276449.3
STAR	ENST00000522050.1	TSL:5	c.399+20A>G	intron	N/A	ENSP00000429009.1
STAR	ENST00000520114.1	TSL:2	n.952+20A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.976

AC:

148547

AN:

152158

Hom.:

72569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.946

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

0.976

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.935

Gnomad FIN

AF:

0.994

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.990

Gnomad OTH

AF:

0.981

GnomAD2 exomes

AF:

0.981

AC:

246568

AN:

251294

AF XY:

0.980

show subpopulations

Gnomad AFR exome

AF:

0.946

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

0.977

Gnomad EAS exome

AF:

0.997

Gnomad FIN exome

AF:

0.994

Gnomad NFE exome

AF:

0.990

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.986

AC:

1440978

AN:

1461750

Hom.:

710462

Cov.:

AF XY:

0.985

AC XY:

716129

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.944

AC:

31603

AN:

33480

American (AMR)

AF:

0.991

AC:

44322

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.979

AC:

25592

AN:

26136

East Asian (EAS)

AF:

0.989

AC:

39281

AN:

39700

South Asian (SAS)

AF:

0.938

AC:

80875

AN:

86258

European-Finnish (FIN)

AF:

0.994

AC:

52943

AN:

53286

Middle Eastern (MID)

AF:

0.981

AC:

5659

AN:

5768

European-Non Finnish (NFE)

AF:

0.990

AC:

1101419

AN:

1112002

Other (OTH)

AF:

0.982

AC:

59284

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1244

2487

3731

4974

6218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21666

43332

64998

86664

108330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.976

AC:

148652

AN:

152276

Hom.:

72617

Cov.:

AF XY:

0.976

AC XY:

72697

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.946

AC:

39305

AN:

41546

American (AMR)

AF:

0.987

AC:

15092

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.976

AC:

3390

AN:

3472

East Asian (EAS)

AF:

0.995

AC:

5140

AN:

5166

South Asian (SAS)

AF:

0.934

AC:

4505

AN:

4824

European-Finnish (FIN)

AF:

0.994

AC:

10567

AN:

10626

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.990

AC:

67378

AN:

68028

Other (OTH)

AF:

0.980

AC:

2072

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

183

366

550

733

916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.982

Hom.:

13991

Bravo

AF:

0.976

Asia WGS

AF:

0.934

AC:

3251

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Jul 27, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital lipoid adrenal hyperplasia due to STAR deficency

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.0

(source)

DANN

Benign

0.34

PhyloP100

0.058

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over