chr8-38142749-T-C

Position:

• chr8-38142749-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000349.3(STAR):​c.*1524A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,702 control chromosomes in the GnomAD database, including 39,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (39865 hom., cov: 29)
• Consequence: STAR NM_000349.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

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]

ASH2L (HGNC:744): (ASH2 like, histone lysine methyltransferase complex subunit) Enables beta-catenin binding activity and transcription cis-regulatory region binding activity. Contributes to histone methyltransferase activity (H3-K4 specific). Involved in histone H3-K4 methylation; positive regulation of cell population proliferation; and response to estrogen. Acts upstream of or within cellular response to DNA damage stimulus. Located in nucleus. Part of MLL3/4 complex and Set1C/COMPASS complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-38142749-T-C is Benign according to our data. Variant chr8-38142749-T-C is described in ClinVar as [Benign]. Clinvar id is 362826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAR	NM_000349.3	c.*1524A>G		3_prime_UTR_variant	7/7	ENST00000276449.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAR	ENST00000276449.9	c.*1524A>G		3_prime_UTR_variant	7/7	1	NM_000349.3	P1
ASH2L	ENST00000521808.5	c.*5-990T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.705 AC: 106856 AN: 151584 Hom.: 39864 Cov.: 29

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.947

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.705 AC: 106883 AN: 151702 Hom.: 39865 Cov.: 29 AF XY: 0.698 AC XY: 51765 AN XY: 74110

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.740

Alfa AF: 0.767 Hom.: 5463

Bravo AF: 0.698

Asia WGS AF: 0.452 AC: 1576 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital lipoid adrenal hyperplasia due to STAR deficency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.73
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3990403; hg19: chr8-38000267;