dbSNP rs7795499: STARD3NL:c.650-5C>T (chr7-38228794-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Variant links:

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]

STARD3NL links:

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ACMG classification

Classification was made for transcript

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 link	c.650-5C>T		splice_region_variant, intron_variant	Intron 7 of 8	ENST00000009041.12	NP_114405.1	O95772-1A0A024RA89

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
STARD3NL	ENST00000009041.12 link	c.650-5C>T	splice_region_variant, intron_variant	Intron 7 of 8	1	NM_032016.4	ENSP00000009041.7	O95772-1
STARD3NL	ENST00000396013.5 link	c.650-5C>T	splice_region_variant, intron_variant	Intron 8 of 9	5		ENSP00000379334.1	O95772-1
STARD3NL	ENST00000434197.5 link	c.596-5C>T	splice_region_variant, intron_variant	Intron 6 of 7	5		ENSP00000394000.1	C9JKL2
STARD3NL	ENST00000471550.1 link	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.459

AC XY:

332250

AN XY:

723164

show subpopulations

Gnomad4 AFR exome

AF:

0.336

AC:

11186

AN:

33336

Gnomad4 AMR exome

AF:

0.525

AC:

23421

AN:

44634

Gnomad4 ASJ exome

AF:

0.493

AC:

12830

AN:

26000

Gnomad4 EAS exome

AF:

0.546

AC:

21567

AN:

39524

Gnomad4 SAS exome

AF:

0.487

AC:

41808

AN:

85828

Gnomad4 FIN exome

AF:

0.451

AC:

23864

AN:

52960

Gnomad4 NFE exome

AF:

0.455

AC:

502654

AN:

1104956

Gnomad4 Remaining exome

AF:

0.451

AC:

27074

AN:

60090

Heterozygous variant carriers

16083

32166

48249

64332

80415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

15132

30264

45396

60528

75660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.428

AC:

65099

AN:

152018

Hom.:

14251

Cov.:

AF XY:

0.433

AC XY:

32160

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.338

AC:

0.338357

AN:

0.338357

Gnomad4 AMR

AF:

0.494

AC:

0.493715

AN:

0.493715

Gnomad4 ASJ

AF:

0.502

AC:

0.502304

AN:

0.502304

Gnomad4 EAS

AF:

0.496

AC:

0.495748

AN:

0.495748

Gnomad4 SAS

AF:

0.480

AC:

0.4801

AN:

0.4801

Gnomad4 FIN

AF:

0.451

AC:

0.450731

AN:

0.450731

Gnomad4 NFE

AF:

0.454

AC:

0.454311

AN:

0.454311

Gnomad4 OTH

AF:

0.421

AC:

0.420627

AN:

0.420627

Heterozygous variant carriers

1905

3810

5714

7619

9524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

616

1232

1848

2464

3080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over