Variant 19-5649932-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000588852.2(SAFB):c.1155C>T(p.Pro385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,613,702 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 38 hom., cov: 31)

Exomes 𝑓: 0.0037 ( 160 hom. )

Consequence

SAFB
ENST00000588852.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

SAFB (HGNC:10520): (scaffold attachment factor B) This gene encodes a DNA-binding protein which has high specificity for scaffold or matrix attachment region DNA elements (S/MAR DNA). This protein is thought to be involved in attaching the base of chromatin loops to the nuclear matrix but there is conflicting evidence as to whether this protein is a component of chromatin or a nuclear matrix protein. Scaffold attachment factors are a specific subset of nuclear matrix proteins (NMP) that specifically bind to S/MAR. The encoded protein is thought to serve as a molecular base to assemble a 'transcriptosome complex' in the vicinity of actively transcribed genes. It is involved in the regulation of heat shock protein 27 transcription, can act as an estrogen receptor co-repressor and is a candidate for breast tumorigenesis. This gene is arranged head-to-head with a similar gene whose product has the same functions. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

SAFB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 19-5649932-C-T is Benign according to our data. Variant chr19-5649932-C-T is described in ClinVar as [Benign]. Clinvar id is 735932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

BS2

High AC in GnomAd4 at 1026 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAFB	NM_001201338.2 linkuse as main transcript	c.1155C>T	p.Pro385=	synonymous_variant	8/21	ENST00000588852.2	NP_001188267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAFB	ENST00000588852.2 linkuse as main transcript	c.1155C>T	p.Pro385=	synonymous_variant	8/21	1	NM_001201338.2	ENSP00000467423	P5	Q15424-3

Frequencies

GnomAD3 genomes

AF:

0.00674

AC:

1026

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.0773

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00847

AC:

2131

AN:

251452

Hom.:

AF XY:

0.00829

AC XY:

1126

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0103

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.0738

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00994

GnomAD4 exome

AF:

0.00366

AC:

5349

AN:

1461468

Hom.:

160

Cov.:

AF XY:

0.00362

AC XY:

2634

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0109

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.0725

Gnomad4 NFE exome

AF:

0.000596

Gnomad4 OTH exome

AF:

0.00404

GnomAD4 genome

AF:

0.00674

AC:

1026

AN:

152234

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

752

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0106

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.0773

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.000914

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.3

DANN

Benign

0.62

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over