rs7795499

Positions:

• chr7-38228794-C-T

Variant summary

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

The NM_032016.4(STARD3NL):​c.650-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,605,086 control chromosomes in the GnomAD database, including 169,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14251 hom., cov: 33)
  • Exomes 𝑓: 0.46 (154759 hom.)
• Consequence: STARD3NL NM_032016.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002361
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

Genes affected

STARD3NL (HGNC:19169): (STARD3 N-terminal like) This gene encodes a late-endosomal protein that contains a conserved MENTAL (MLN64 N-terminal) domain. The encoded protein binds cholesterol molecules and may play a role in endosomal cholesterol transport through interactions with metastatic lymph node protein 64 (MLN64). [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STARD3NL	NM_032016.4	c.650-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000009041.12	NP_114405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STARD3NL	ENST00000009041.12	c.650-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032016.4	ENSP00000009041	P1
STARD3NL	ENST00000396013.5	c.650-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000379334	P1
STARD3NL	ENST00000434197.5	c.596-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000394000
STARD3NL	ENST00000471550.1	n.2833-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65048 AN: 151900 Hom.: 14241 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.423

GnomAD3 exomes AF: 0.464 AC: 116183 AN: 250476 Hom.: 27336 AF XY: 0.463 AC XY: 62671 AN XY: 135436

Gnomad AFR exome AF: 0.337

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.472

Gnomad SAS exome AF: 0.485

Gnomad FIN exome AF: 0.451

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.446

GnomAD4 exome AF: 0.459 AC: 666647 AN: 1453068 Hom.: 154759 Cov.: 31 AF XY: 0.459 AC XY: 332250 AN XY: 723164

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.493

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.428 AC: 65099 AN: 152018 Hom.: 14251 Cov.: 33 AF XY: 0.433 AC XY: 32160 AN XY: 74290

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.421

Alfa AF: 0.446 Hom.: 18695

Bravo AF: 0.424

Asia WGS AF: 0.438 AC: 1522 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.57
DANN	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.0
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: rs7795499; hg19: chr7-38268395; COSMIC: COSV50518278;