rs1874224

Positions:

• chr17-39639407-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006804.4(STARD3):​c.-52+2176T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 152,198 control chromosomes in the GnomAD database, including 843 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 0.065 (843 hom., cov: 32)
• Consequence: STARD3 NM_006804.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

Genes affected

STARD3 (HGNC:17579): (StAR related lipid transfer domain containing 3) This gene encodes a member of a subfamily of lipid trafficking proteins that are characterized by a C-terminal steroidogenic acute regulatory domain and an N-terminal metastatic lymph node 64 domain. The encoded protein localizes to the membranes of late endosomes and may be involved in exporting cholesterol. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD3	NM_006804.4	c.-52+2176T>G		intron_variant		ENST00000336308.10	NP_006795.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STARD3	ENST00000336308.10	c.-52+2176T>G		intron_variant		1	NM_006804.4	ENSP00000337446	P1

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9787 AN: 152080 Hom.: 835 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0454

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

GnomAD4 genome AF: 0.0646 AC: 9829 AN: 152198 Hom.: 843 Cov.: 32 AF XY: 0.0626 AC XY: 4662 AN XY: 74422

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.0276

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00462

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0258 Hom.: 192

Bravo AF: 0.0723

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1874224; hg19: chr17-37795660;