19-5649932-C-T

Variant names:

• chr19-5649932-C-T
• rs75289952
• NM_001201338.2:c.1155C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001201338.2(SAFB):​c.1155C>T​(p.Pro385Pro) 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 NM_001201338.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.82

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SAFB	NM_001201338.2	c.1155C>T	p.Pro385Pro	synonymous_variant	Exon 8 of 21	ENST00000588852.2	NP_001188267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB	ENST00000588852.2	c.1155C>T	p.Pro385Pro	synonymous_variant	Exon 8 of 21	1	NM_001201338.2	ENSP00000467423.1

Frequencies

GnomAD3 genomes AF: 0.00674 AC: 1026 AN: 152116 Hom.: 38 Cov.: 31

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

GnomAD2 exomes AF: 0.00847 AC: 2131 AN: 251452 AF XY: 0.00829

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 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.: 30 AF XY: 0.00362 AC XY: 2634 AN XY: 727088

Gnomad4 AFR exome AF: 0.0000896 AC: 3 AN: 33476

Gnomad4 AMR exome AF: 0.0000671 AC: 3 AN: 44724

Gnomad4 ASJ exome AF: 0.0000383 AC: 1 AN: 26132

Gnomad4 EAS exome AF: 0.0109 AC: 431 AN: 39690

Gnomad4 SAS exome AF: 0.00151 AC: 130 AN: 86244

Gnomad4 FIN exome AF: 0.0725 AC: 3872 AN: 53408

Gnomad4 NFE exome AF: 0.000596 AC: 663 AN: 1111652

Gnomad4 Remaining exome AF: 0.00404 AC: 244 AN: 60374

GnomAD4 genome AF: 0.00674 AC: 1026 AN: 152234 Hom.: 38 Cov.: 31 AF XY: 0.0101 AC XY: 752 AN XY: 74422

Gnomad4 AFR AF: 0.0000482 AC: 0.0000481556 AN: 0.0000481556

Gnomad4 AMR AF: 0.0000654 AC: 0.0000653851 AN: 0.0000653851

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.0106 AC: 0.0106342 AN: 0.0106342

Gnomad4 SAS AF: 0.00208 AC: 0.00207727 AN: 0.00207727

Gnomad4 FIN AF: 0.0773 AC: 0.0772642 AN: 0.0772642

Gnomad4 NFE AF: 0.00193 AC: 0.00192562 AN: 0.00192562

Gnomad4 OTH AF: 0.00378 AC: 0.0037843 AN: 0.0037843

Alfa AF: 0.00190 Hom.: 1

Bravo AF: 0.000914

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75289952; hg19: chr19-5649943; COSMIC: COSV52651506; COSMIC: COSV52651506;