NM_005506.4:c.1113+14T>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005506.4(SCARB2):c.1113+14T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,557,634 control chromosomes in the GnomAD database, including 22,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3622 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18913 hom. )

Consequence

SCARB2
NM_005506.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.46

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 links:

ENSG00000286074 (HGNC:):

ENSG00000286074 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 4-76169853-A-T is Benign according to our data. Variant chr4-76169853-A-T is described in ClinVar as [Benign]. Clinvar id is 138968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-76169853-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SCARB2	NM_005506.4 link	c.1113+14T>A	intron_variant	Intron 8 of 11	ENST00000264896.8	NP_005497.1	Q14108-1A0A024RDG6
SCARB2	NM_001204255.2 link	c.684+14T>A	intron_variant	Intron 5 of 8		NP_001191184.1	Q14108-2
SCARB2	XM_047416429.1 link	c.639+14T>A	intron_variant	Intron 8 of 11		XP_047272385.1
SCARB2	XM_047416430.1 link	c.639+14T>A	intron_variant	Intron 8 of 11		XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8 link	c.1113+14T>A		intron_variant	Intron 8 of 11	1	NM_005506.4	ENSP00000264896.2		Q14108-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30913

AN:

152020

Hom.:

3607

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.190

GnomAD3 exomes

AF:

0.177

AC:

44539

AN:

251288

Hom.:

4583

AF XY:

0.174

AC XY:

23590

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.349

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.157

AC:

220068

AN:

1405496

Hom.:

18913

Cov.:

AF XY:

0.157

AC XY:

110478

AN XY:

702776

show subpopulations

Gnomad4 AFR exome

AF:

0.321

Gnomad4 AMR exome

AF:

0.150

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.203

AC:

30950

AN:

152138

Hom.:

3622

Cov.:

AF XY:

0.203

AC XY:

15081

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.192

Alfa

AF:

0.103

Hom.:

195

Bravo

AF:

0.210

Asia WGS

AF:

0.253

AC:

879

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 11, 2013

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. -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 30% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 28. Only high quality variants are reported. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Progressive myoclonic epilepsy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.87

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over