4-76189212-C-G

Position:

• chr4-76189212-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SCARB2	NM_005506.4	c.275+6495G>C		intron_variant		ENST00000264896.8	NP_005497.1
SCARB2	NM_001204255.2	c.275+6495G>C		intron_variant			NP_001191184.1
SCARB2	XM_047416429.1	c.-200+6495G>C		intron_variant			XP_047272385.1
SCARB2	XM_047416430.1	c.-200+6495G>C		intron_variant			XP_047272386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARB2	ENST00000264896.8	c.275+6495G>C		intron_variant		1	NM_005506.4	ENSP00000264896	P4
	ENST00000651366.1	n.103-10754C>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.334

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

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

Other links and lift over

dbSNP: rs6825004; hg19: chr4-77110365;