NM_005506.4:c.275+6495G>C

Variant names:

• chr4-76189212-C-G
• rs6825004
• NM_005506.4:c.275+6495G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005506.4(SCARB2):​c.275+6495G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,038 control chromosomes in the GnomAD database, including 7,071 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7071 hom., cov: 32)
• Consequence: SCARB2 NM_005506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 28 publications found

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

ENSG00000286074 (HGNC:58820):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARB2	NM_005506.4	c.275+6495G>C		intron_variant	Intron 2 of 11	ENST00000264896.8	NP_005497.1
SCARB2	NM_001204255.2	c.275+6495G>C		intron_variant	Intron 2 of 8		NP_001191184.1
SCARB2	XM_047416429.1	c.-200+6495G>C		intron_variant	Intron 2 of 11		XP_047272385.1
SCARB2	XM_047416430.1	c.-200+6495G>C		intron_variant	Intron 2 of 11		XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8	c.275+6495G>C		intron_variant	Intron 2 of 11	1	NM_005506.4	ENSP00000264896.2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44757 AN: 151920 Hom.: 7071 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44755 AN: 152038 Hom.: 7071 Cov.: 32 AF XY: 0.293 AC XY: 21784 AN XY: 74322

African (AFR) AF: 0.205 AC: 8509 AN: 41472

American (AMR) AF: 0.464 AC: 7078 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1881 AN: 5172

South Asian (SAS) AF: 0.237 AC: 1140 AN: 4820

European-Finnish (FIN) AF: 0.245 AC: 2584 AN: 10558

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20994 AN: 67974

Other (OTH) AF: 0.334 AC: 705 AN: 2112

Alfa AF: 0.175 Hom.: 360

Bravo AF: 0.312

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.3
DANN	Benign	0.87
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6825004; hg19: chr4-77110365;