chr17-39639407-T-G

Variant names:

• chr17-39639407-T-G
• rs1874224
• NM_006804.4:c.-52+2176T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
STARD3	NM_006804.4	c.-52+2176T>G		intron_variant	Intron 1 of 14	ENST00000336308.10	NP_006795.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD3	ENST00000336308.10	c.-52+2176T>G		intron_variant	Intron 1 of 14	1	NM_006804.4	ENSP00000337446.5

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

African (AFR) AF: 0.200 AC: 8281 AN: 41478

American (AMR) AF: 0.0276 AC: 422 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4830

European-Finnish (FIN) AF: 0.00462 AC: 49 AN: 10596

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 904 AN: 68014

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0329 Hom.: 389

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
PhyloP100		-0.21
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: rs1874224; hg19: chr17-37795660;