chr4-76161971-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005506.4(SCARB2):c.1399-220G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 612,698 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 109 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 76 hom. )

Consequence

SCARB2
NM_005506.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.227

Publications

0 publications found

Variant links:

Genes affected

SCARB2 (HGNC:1665): (scavenger receptor class B member 2) The protein encoded by this gene is a type III glycoprotein that is located primarily in limiting membranes of lysosomes and endosomes. Earlier studies in mice and rat suggested that this protein may participate in membrane transportation and the reorganization of endosomal/lysosomal compartment. The protein deficiency in mice was reported to impair cell membrane transport processes and cause pelvic junction obstruction, deafness, and peripheral neuropathy. Further studies in human showed that this protein is a ubiquitously expressed protein and that it is involved in the pathogenesis of HFMD (hand, foot, and mouth disease) caused by enterovirus-71 and possibly by coxsackievirus A16. Mutations in this gene caused an autosomal recessive progressive myoclonic epilepsy-4 (EPM4), also known as action myoclonus-renal failure syndrome (AMRF). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

SCARB2 Gene-Disease associations (from GenCC):

action myoclonus-renal failure syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
progressive myoclonus epilepsy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Unverricht-Lundborg syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SCARB2 links:

ENSG00000286074 (HGNC:):

ENSG00000286074 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-76161971-C-A is Benign according to our data. Variant chr4-76161971-C-A is described in ClinVar as [Benign]. Clinvar id is 673157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SCARB2	NM_005506.4 link	c.1399-220G>T	intron_variant	Intron 11 of 11	ENST00000264896.8	NP_005497.1	Q14108-1A0A024RDG6
SCARB2	NM_001204255.2 link	c.970-220G>T	intron_variant	Intron 8 of 8		NP_001191184.1	Q14108-2
SCARB2	XM_047416429.1 link	c.925-220G>T	intron_variant	Intron 11 of 11		XP_047272385.1
SCARB2	XM_047416430.1 link	c.925-220G>T	intron_variant	Intron 11 of 11		XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8 link	c.1399-220G>T		intron_variant	Intron 11 of 11	1	NM_005506.4	ENSP00000264896.2		Q14108-1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3516

AN:

152044

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0714

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0505

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0186

GnomAD4 exome

AF:

0.00691

AC:

3182

AN:

460536

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

1549

AN XY:

245364

show subpopulations

African (AFR)

AF:

0.0696

AC:

900

AN:

12940

American (AMR)

AF:

0.00484

AC:

115

AN:

23738

Ashkenazi Jewish (ASJ)

AF:

0.00140

AC:

AN:

14270

East Asian (EAS)

AF:

0.0462

AC:

1408

AN:

30458

South Asian (SAS)

AF:

0.00305

AC:

147

AN:

48234

European-Finnish (FIN)

AF:

0.000763

AC:

AN:

28832

Middle Eastern (MID)

AF:

0.0112

AC:

AN:

2326

European-Non Finnish (NFE)

AF:

0.00110

AC:

300

AN:

273344

Other (OTH)

AF:

0.00924

AC:

244

AN:

26394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

155

309

464

618

773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0232

AC:

3528

AN:

152162

Hom.:

109

Cov.:

AF XY:

0.0229

AC XY:

1704

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0714

AC:

2961

AN:

41466

American (AMR)

AF:

0.00955

AC:

146

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.0506

AC:

262

AN:

5180

South Asian (SAS)

AF:

0.00601

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000849

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00110

AC:

AN:

68018

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

161

322

484

645

806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0189

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.6

(source)

DANN

Benign

0.55

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr4-76161971-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over