Variant 4-76162031-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005506.4(SCARB2):c.1399-280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 507,224 control chromosomes in the GnomAD database, including 706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 184 hom., cov: 32)

Exomes 𝑓: 0.049 ( 522 hom. )

Consequence

SCARB2
NM_005506.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.178

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-76162031-G-A is Benign according to our data. Variant chr4-76162031-G-A is described in ClinVar as [Benign]. Clinvar id is 668971.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SCARB2	NM_005506.4 linkuse as main transcript	c.1399-280C>T	intron_variant	ENST00000264896.8
SCARB2	NM_001204255.2 linkuse as main transcript	c.970-280C>T	intron_variant
SCARB2	XM_047416429.1 linkuse as main transcript	c.925-280C>T	intron_variant
SCARB2	XM_047416430.1 linkuse as main transcript	c.925-280C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB2	ENST00000264896.8 linkuse as main transcript	c.1399-280C>T		intron_variant		1	NM_005506.4	P4	Q14108-1
	ENST00000651366.1 linkuse as main transcript	n.102+12765G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6261

AN:

152096

Hom.:

184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.0375

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0595

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0613

Gnomad OTH

AF:

0.0411

GnomAD4 exome

AF:

0.0488

AC:

17338

AN:

355010

Hom.:

522

Cov.:

AF XY:

0.0479

AC XY:

8972

AN XY:

187240

show subpopulations

Gnomad4 AFR exome

AF:

0.00907

Gnomad4 AMR exome

AF:

0.0318

Gnomad4 ASJ exome

AF:

0.00927

Gnomad4 EAS exome

AF:

0.000171

Gnomad4 SAS exome

AF:

0.0337

Gnomad4 FIN exome

AF:

0.0524

Gnomad4 NFE exome

AF:

0.0620

Gnomad4 OTH exome

AF:

0.0495

GnomAD4 genome

AF:

0.0411

AC:

6260

AN:

152214

Hom.:

184

Cov.:

AF XY:

0.0416

AC XY:

3097

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.0374

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0300

Gnomad4 FIN

AF:

0.0595

Gnomad4 NFE

AF:

0.0613

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0492

Hom.:

Bravo

AF:

0.0386

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.4

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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