Genetic Variant SCARB2:c.*117G>A (chr4-76161596-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_005506.4(SCARB2):c.*117G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00804 in 1,058,144 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 110 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 112 hom. )

Consequence

SCARB2
NM_005506.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.90

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=-1.01).

BP6

Variant 4-76161596-C-T is Benign according to our data. Variant chr4-76161596-C-T is described in ClinVar as [Benign]. Clinvar id is 1247776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SCARB2	NM_005506.4 link	c.*117G>A	3_prime_UTR_variant	Exon 12 of 12	ENST00000264896.8	NP_005497.1	Q14108-1A0A024RDG6
SCARB2	NM_001204255.2 link	c.*117G>A	3_prime_UTR_variant	Exon 9 of 9		NP_001191184.1	Q14108-2
SCARB2	XM_047416429.1 link	c.*117G>A	3_prime_UTR_variant	Exon 12 of 12		XP_047272385.1
SCARB2	XM_047416430.1 link	c.*117G>A	3_prime_UTR_variant	Exon 12 of 12		XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896 link	c.*117G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_005506.4	ENSP00000264896.2		Q14108-1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3603

AN:

152124

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0732

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.0503

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.0187

GnomAD4 exome

AF:

0.00540

AC:

4890

AN:

905902

Hom.:

112

Cov.:

AF XY:

0.00504

AC XY:

2384

AN XY:

472914

show subpopulations

Gnomad4 AFR exome

AF:

0.0740

Gnomad4 AMR exome

AF:

0.00427

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.0481

Gnomad4 SAS exome

AF:

0.00293

Gnomad4 FIN exome

AF:

0.000783

Gnomad4 NFE exome

AF:

0.000900

Gnomad4 OTH exome

AF:

0.00877

GnomAD4 genome

AF:

0.0237

AC:

3615

AN:

152242

Hom.:

110

Cov.:

AF XY:

0.0234

AC XY:

1741

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0733

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.0504

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.0190

Alfa

AF:

0.00533

Hom.:

Bravo

AF:

0.0271

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

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

-1.0

CADD

Benign

0.014

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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