dbSNP rs2267443: SREBF2:c.2209-1667A>G (chr22-41891450-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004599.4(SREBF2):c.2209-1667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,982 control chromosomes in the GnomAD database, including 34,247 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 0.67 ( 34245 hom., cov: 31)

Exomes 𝑓: 0.64 ( 2 hom. )

Consequence

SREBF2
NM_004599.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

17 publications found

Variant links:

Genes affected

SREBF2 (HGNC:11290): (sterol regulatory element binding transcription factor 2) This gene encodes a member of the a ubiquitously expressed transcription factor that controls cholesterol homeostasis by regulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix-leucine zipper (bHLH-Zip) domain and binds the sterol regulatory element 1 motif. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

SREBF2 Gene-Disease associations (from GenCC):

neurocutaneous syndrome
Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hereditary spastic paraplegia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SREBF2 links:

Genome browser will be placed here

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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004599.4. 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
	SREBF2	NM_004599.4	MANE Select	c.2209-1667A>G		intron	N/A	NP_004590.2
	SREBF2	NR_103834.2		n.2475-1667A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SREBF2	ENST00000361204.9	TSL:1 MANE Select	c.2209-1667A>G	intron	N/A	ENSP00000354476.4	Q12772-1
SREBF2	ENST00000424354.5	TSL:1	n.*254-1667A>G	intron	N/A	ENSP00000395728.1	G3V0I8
SREBF2	ENST00000491541.1	TSL:1	n.759+51A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.666

AC:

101117

AN:

151850

Hom.:

34199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.694

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.681

Gnomad SAS

AF:

0.579

Gnomad FIN

AF:

0.599

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.607

GnomAD4 exome

AF:

0.643

AC:

AN:

Hom.:

AF XY:

0.600

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.666

AC:

101214

AN:

151968

Hom.:

34245

Cov.:

AF XY:

0.665

AC XY:

49408

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.770

AC:

31927

AN:

41458

American (AMR)

AF:

0.713

AC:

10894

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

2261

AN:

3470

East Asian (EAS)

AF:

0.680

AC:

3500

AN:

5148

South Asian (SAS)

AF:

0.578

AC:

2790

AN:

4824

European-Finnish (FIN)

AF:

0.599

AC:

6315

AN:

10550

Middle Eastern (MID)

AF:

0.616

AC:

181

AN:

294

European-Non Finnish (NFE)

AF:

0.610

AC:

41444

AN:

67932

Other (OTH)

AF:

0.605

AC:

1275

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1671

3342

5014

6685

8356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.631

Hom.:

58996

Bravo

AF:

0.684

Asia WGS

AF:

0.626

AC:

2176

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.32

(source)

DANN

Benign

0.66

PhyloP100

-1.2

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