rs7795499

Variant names:

• chr7-38228794-C-T
• rs7795499
• NM_032016.4:c.650-5C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032016.4(STARD3NL):​c.650-5C>T variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00002361
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
STARD3NL	NM_032016.4	c.650-5C>T		splice_region_variant, intron_variant	Intron 7 of 8	ENST00000009041.12	NP_114405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STARD3NL	ENST00000009041.12	c.650-5C>T		splice_region_variant, intron_variant	Intron 7 of 8	1	NM_032016.4	ENSP00000009041.7
STARD3NL	ENST00000396013.5	c.650-5C>T		splice_region_variant, intron_variant	Intron 8 of 9	5		ENSP00000379334.1
STARD3NL	ENST00000434197.5	c.596-5C>T		splice_region_variant, intron_variant	Intron 6 of 7	5		ENSP00000394000.1
STARD3NL	ENST00000471550.1	n.2833-5C>T		splice_region_variant, intron_variant	Intron 5 of 6	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

GnomAD2 exomes AF: 0.464 AC: 116183 AN: 250476 AF XY: 0.463

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 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

African (AFR) AF: 0.336 AC: 11186 AN: 33336

American (AMR) AF: 0.525 AC: 23421 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 12830 AN: 26000

East Asian (EAS) AF: 0.546 AC: 21567 AN: 39524

South Asian (SAS) AF: 0.487 AC: 41808 AN: 85828

European-Finnish (FIN) AF: 0.451 AC: 23864 AN: 52960

Middle Eastern (MID) AF: 0.391 AC: 2243 AN: 5740

European-Non Finnish (NFE) AF: 0.455 AC: 502654 AN: 1104956

Other (OTH) AF: 0.451 AC: 27074 AN: 60090

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

African (AFR) AF: 0.338 AC: 14033 AN: 41474

American (AMR) AF: 0.494 AC: 7541 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1744 AN: 3472

East Asian (EAS) AF: 0.496 AC: 2565 AN: 5174

South Asian (SAS) AF: 0.480 AC: 2316 AN: 4824

European-Finnish (FIN) AF: 0.451 AC: 4748 AN: 10534

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30875 AN: 67960

Other (OTH) AF: 0.421 AC: 885 AN: 2104

Alfa AF: 0.446 Hom.: 21619

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
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7795499; hg19: chr7-38268395; COSMIC: COSV50518278;