Genetic Variant NM_005505.5:c.1401+1580T>G (chr12-124784777-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005505.5(SCARB1):c.1401+1580T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,320 control chromosomes in the GnomAD database, including 31,749 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 0.64 ( 31706 hom., cov: 33)

Exomes 𝑓: 0.66 ( 43 hom. )

Consequence

SCARB1
NM_005505.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.217

Publications

7 publications found

Variant links:

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]

SCARB1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.741 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCARB1	NM_005505.5	MANE Select	c.1401+1580T>G	intron	N/A	NP_005496.4
SCARB1	NM_001367981.1		c.1651+1330T>G	intron	N/A	NP_001354910.1	Q8WTV0-1
SCARB1	NM_001367983.1		c.1407+1580T>G	intron	N/A	NP_001354912.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCARB1	ENST00000261693.11	TSL:1 MANE Select	c.1401+1580T>G	intron	N/A	ENSP00000261693.6	Q8WTV0-2
SCARB1	ENST00000546215.5	TSL:1	c.1317+1664T>G	intron	N/A	ENSP00000442862.1	B7ZKQ9
SCARB1	ENST00000535005.5	TSL:1	n.1716+1580T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97334

AN:

152000

Hom.:

31698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.760

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.687

Gnomad OTH

AF:

0.628

GnomAD4 exome

AF:

0.663

AC:

134

AN:

202

Hom.:

Cov.:

AF XY:

0.667

AC XY:

100

AN XY:

150

show subpopulations

African (AFR)

AF:

0.833

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.375

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.674

AC:

120

AN:

178

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.640

AC:

97370

AN:

152118

Hom.:

31706

Cov.:

AF XY:

0.638

AC XY:

47410

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.614

AC:

25465

AN:

41496

American (AMR)

AF:

0.532

AC:

8131

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

2472

AN:

3470

East Asian (EAS)

AF:

0.368

AC:

1898

AN:

5154

South Asian (SAS)

AF:

0.762

AC:

3678

AN:

4828

European-Finnish (FIN)

AF:

0.640

AC:

6780

AN:

10590

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.687

AC:

46704

AN:

67966

Other (OTH)

AF:

0.626

AC:

1323

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1825

3651

5476

7302

9127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.673

Hom.:

148539

Bravo

AF:

0.628

Asia WGS

AF:

0.572

AC:

1990

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

3.4

(source)

DANN

Benign

0.49

PhyloP100

0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over