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):

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SREBF2	NM_004599.4 link	c.2209-1667A>G		intron_variant	Intron 11 of 18	ENST00000361204.9	NP_004590.2	Q12772-1A0A024R1Q0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SREBF2	ENST00000361204.9 link	c.2209-1667A>G	intron_variant	Intron 11 of 18	1	NM_004599.4	ENSP00000354476.4	Q12772-1
SREBF2	ENST00000424354.5 link	n.*254-1667A>G	intron_variant	Intron 12 of 21	1		ENSP00000395728.1	G3V0I8
SREBF2	ENST00000491541.1 link	n.759+51A>G	intron_variant	Intron 3 of 12	1
SREBF2	ENST00000710853.1 link	c.2119-1667A>G	intron_variant	Intron 11 of 18			ENSP00000518526.1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over