Genetic Variant SBF2:c.-485G>T (chr11-10303778-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001424318.1(SBF2):c.-485G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,172 control chromosomes in the GnomAD database, including 13,336 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 0.41 ( 13323 hom., cov: 33)

Exomes 𝑓: 0.48 ( 13 hom. )

Consequence

SBF2
NM_001424318.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.349

Publications

17 publications found

Variant links:

Genes affected

SBF2 (HGNC:2135): (SET binding factor 2) This gene encodes a pseudophosphatase and member of the myotubularin-related protein family. This gene maps within the CMT4B2 candidate region of chromosome 11p15 and mutations in this gene have been associated with Charcot-Marie-Tooth Disease, type 4B2. [provided by RefSeq, Jul 2008]

SBF2 links:

ADM (HGNC:259): (adrenomedullin) The protein encoded by this gene is a preprohormone which is cleaved to form two biologically active peptides, adrenomedullin and proadrenomedullin N-terminal 20 peptide. Adrenomedullin is a 52 aa peptide with several functions, including vasodilation, regulation of hormone secretion, promotion of angiogenesis, and antimicrobial activity. The antimicrobial activity is antibacterial, as the peptide has been shown to kill E. coli and S. aureus at low concentration. [provided by RefSeq, Aug 2014]

ADM links:

ADM-DT (HGNC:55516): (ADM divergent transcript)

ADM-DT 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424318.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
SBF2	NM_001424318.1	c.-485G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 41	NP_001411247.1
SBF2	NM_001424318.1	c.-485G>T	5_prime_UTR	Exon 1 of 41	NP_001411247.1
SBF2	NM_001425070.1	c.-3+722G>T	intron	N/A	NP_001411999.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADM	ENST00000879128.1		c.-110+121C>A	intron	N/A	ENSP00000549187.1
ADM-DT	ENST00000526906.2	TSL:2	n.79G>T	non_coding_transcript_exon	Exon 1 of 2
ADM-DT	ENST00000847672.1		n.77G>T	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61972

AN:

151958

Hom.:

13309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.479

AC:

AN:

Hom.:

AF XY:

0.469

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.515

AC:

AN:

Other (OTH)

AF:

0.300

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.408

AC:

62029

AN:

152076

Hom.:

13323

Cov.:

AF XY:

0.409

AC XY:

30379

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.301

AC:

12510

AN:

41496

American (AMR)

AF:

0.428

AC:

6537

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1347

AN:

3466

East Asian (EAS)

AF:

0.275

AC:

1416

AN:

5156

South Asian (SAS)

AF:

0.322

AC:

1553

AN:

4818

European-Finnish (FIN)

AF:

0.504

AC:

5323

AN:

10570

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.473

AC:

32148

AN:

67964

Other (OTH)

AF:

0.391

AC:

826

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1872

3744

5615

7487

9359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.431

Hom.:

24944

Bravo

AF:

0.395

Asia WGS

AF:

0.257

AC:

893

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.8

(source)

DANN

Benign

0.46

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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