12-124807867-G-A

Variant names:

• chr12-124807867-G-A
• rs5892
• NM_005505.5:c.903C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005505.5(SCARB1):​c.903C>T​(p.Phe301Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,072 control chromosomes in the GnomAD database, including 414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (121 hom., cov: 32)
  • Exomes 𝑓: 0.011 (293 hom.)
• Consequence: SCARB1 NM_005505.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0290
• Publications: 18 publications found

Genes affected

SCARB1 (HGNC:1664): (scavenger receptor class B member 1) The protein encoded by this gene is a plasma membrane receptor for high density lipoprotein cholesterol (HDL). The encoded protein mediates cholesterol transfer to and from HDL. In addition, this protein is a receptor for hepatitis C virus glycoprotein E2 and facilitates cell entry by the virus, SARS-CoV2. [provided by RefSeq, Oct 2021]

ENSG00000287242 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 12-124807867-G-A is Benign according to our data. Variant chr12-124807867-G-A is described in ClinVar as Benign. ClinVar VariationId is 1224092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.029 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005505.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	NM_005505.5	MANE Select	c.903C>T	p.Phe301Phe	synonymous	Exon 7 of 13	NP_005496.4
	SCARB1	NM_001367981.1		c.903C>T	p.Phe301Phe	synonymous	Exon 7 of 12	NP_001354910.1
	SCARB1	NM_001367982.1		c.780C>T	p.Phe260Phe	synonymous	Exon 7 of 11	NP_001354911.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.903C>T	p.Phe301Phe	synonymous	Exon 7 of 13	ENSP00000261693.6
	SCARB1	ENST00000546215.5	TSL:1	c.903C>T	p.Phe301Phe	synonymous	Exon 7 of 13	ENSP00000442862.1
	SCARB1	ENST00000535005.5	TSL:1	n.1218C>T		non_coding_transcript_exon	Exon 8 of 13

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3932 AN: 152126 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00575

Gnomad OTH AF: 0.0216

GnomAD2 exomes AF: 0.0177 AC: 4450 AN: 251478 AF XY: 0.0180

Gnomad AFR exome AF: 0.0675

Gnomad AMR exome AF: 0.00610

Gnomad ASJ exome AF: 0.0135

Gnomad EAS exome AF: 0.0421

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.00667

Gnomad OTH exome AF: 0.0138

GnomAD4 exome AF: 0.0108 AC: 15782 AN: 1461828 Hom.: 293 Cov.: 32 AF XY: 0.0116 AC XY: 8423 AN XY: 727216

African (AFR) AF: 0.0780 AC: 2613 AN: 33480

American (AMR) AF: 0.00713 AC: 319 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 354 AN: 26136

East Asian (EAS) AF: 0.0284 AC: 1126 AN: 39700

South Asian (SAS) AF: 0.0424 AC: 3657 AN: 86254

European-Finnish (FIN) AF: 0.00110 AC: 59 AN: 53418

Middle Eastern (MID) AF: 0.0194 AC: 112 AN: 5768

European-Non Finnish (NFE) AF: 0.00577 AC: 6421 AN: 1111954

Other (OTH) AF: 0.0186 AC: 1121 AN: 60394

GnomAD4 genome AF: 0.0261 AC: 3967 AN: 152244 Hom.: 121 Cov.: 32 AF XY: 0.0264 AC XY: 1963 AN XY: 74430

African (AFR) AF: 0.0692 AC: 2874 AN: 41544

American (AMR) AF: 0.00849 AC: 130 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3472

East Asian (EAS) AF: 0.0400 AC: 206 AN: 5156

South Asian (SAS) AF: 0.0487 AC: 235 AN: 4824

European-Finnish (FIN) AF: 0.00141 AC: 15 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00575 AC: 391 AN: 68016

Other (OTH) AF: 0.0237 AC: 50 AN: 2106

Alfa AF: 0.0138 Hom.: 68

Bravo AF: 0.0281

Asia WGS AF: 0.0610 AC: 210 AN: 3478

EpiCase AF: 0.00562

EpiControl AF: 0.00788

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Oct 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		0.029
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: rs5892; hg19: chr12-125292413;