rs199895330

Positions:

chr4-76195811-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005506.4(SCARB2):c.171T>C(p.Pro57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,613,828 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 26 hom. )

Consequence

SCARB2
NM_005506.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.621

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-76195811-A-G is Benign according to our data. Variant chr4-76195811-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 259781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.621 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00222 (338/152352) while in subpopulation EAS AF= 0.00135 (7/5188). AF 95% confidence interval is 0.00069. There are 8 homozygotes in gnomad4. There are 248 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SCARB2	NM_005506.4 linkuse as main transcript	c.171T>C	p.Pro57=	synonymous_variant	2/12	ENST00000264896.8
SCARB2	NM_001204255.2 linkuse as main transcript	c.171T>C	p.Pro57=	synonymous_variant	2/9
SCARB2	XM_047416429.1 linkuse as main transcript	c.-304T>C		5_prime_UTR_variant	2/12
SCARB2	XM_047416430.1 linkuse as main transcript	c.-304T>C		5_prime_UTR_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARB2	ENST00000264896.8 linkuse as main transcript	c.171T>C	p.Pro57=	synonymous_variant	2/12	1	NM_005506.4	P4	Q14108-1
	ENST00000651366.1 linkuse as main transcript	n.103-4155A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00222

AC:

338

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00288

AC:

725

AN:

251322

Hom.:

AF XY:

0.00278

AC XY:

378

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0263

Gnomad NFE exome

AF:

0.000950

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00115

AC:

1686

AN:

1461476

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

827

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0257

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00222

AC:

338

AN:

152352

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

248

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0254

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000200

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2015	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. -

Action myoclonus-renal failure syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 27, 2021

- -

Progressive myoclonic epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.8

DANN

Benign

0.63

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