12-124863709-G-A

Variant names:

• chr12-124863709-G-A
• rs2070242
• NM_005505.5:c.12C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005505.5(SCARB1):​c.12C>T​(p.Ser4Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00527 in 1,529,510 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (194 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (159 hom.)
• Consequence: SCARB1 NM_005505.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.396
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 12-124863709-G-A is Benign according to our data. Variant chr12-124863709-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.396 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0931 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	NM_005505.5	MANE Select	c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 13	NP_005496.4
	SCARB1	NM_001367981.1		c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 12	NP_001354910.1
	SCARB1	NM_001367983.1		c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 13	NP_001354912.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 13	ENSP00000261693.6
	SCARB1	ENST00000546215.5	TSL:1	c.12C>T	p.Ser4Ser	synonymous	Exon 1 of 13	ENSP00000442862.1
	SCARB1	ENST00000535005.5	TSL:1	n.441+3280C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4217 AN: 152100 Hom.: 194 Cov.: 33

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.00440 AC: 559 AN: 126998 AF XY: 0.00329

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00456

Gnomad ASJ exome AF: 0.00188

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000375

Gnomad OTH exome AF: 0.00606

GnomAD4 exome AF: 0.00279 AC: 3838 AN: 1377302 Hom.: 159 Cov.: 31 AF XY: 0.00241 AC XY: 1640 AN XY: 679980

African (AFR) AF: 0.103 AC: 2915 AN: 28266

American (AMR) AF: 0.00481 AC: 163 AN: 33860

Ashkenazi Jewish (ASJ) AF: 0.00228 AC: 55 AN: 24132

East Asian (EAS) AF: 0.00 AC: 0 AN: 33126

South Asian (SAS) AF: 0.000207 AC: 16 AN: 77278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48340

Middle Eastern (MID) AF: 0.00767 AC: 43 AN: 5604

European-Non Finnish (NFE) AF: 0.000260 AC: 278 AN: 1069748

Other (OTH) AF: 0.00646 AC: 368 AN: 56948

GnomAD4 genome AF: 0.0278 AC: 4225 AN: 152208 Hom.: 194 Cov.: 33 AF XY: 0.0267 AC XY: 1987 AN XY: 74428

African (AFR) AF: 0.0956 AC: 3971 AN: 41552

American (AMR) AF: 0.0104 AC: 159 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 67958

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.00916 Hom.: 21

Bravo AF: 0.0313

Asia WGS AF: 0.00754 AC: 28 AN: 3464

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	SCARB1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.2
DANN	Benign	0.96
PhyloP100		-0.40
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2070242; hg19: chr12-125348255; COSMIC: COSV108751133;