rs806706

Positions:

• chr19-5610034-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_014649.3(SAFB2):​c.1257C>T​(p.Arg419=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,614,052 control chromosomes in the GnomAD database, including 743 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 0.023 (62 hom., cov: 31)
  • Exomes 𝑓: 0.028 (681 hom.)
• Consequence: SAFB2 NM_014649.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

Genes affected

SAFB2 (HGNC:21605): (scaffold attachment factor B2) The protein encoded by this gene, along with its paralog (scaffold attachment factor B1), is a repressor of estrogen receptor alpha. The encoded protein binds scaffold/matrix attachment region (S/MAR) DNA and is involved in cell cycle regulation, apoptosis, differentiation, the stress response, and regulation of immune genes. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.364 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0234 (3557/152268) while in subpopulation NFE AF= 0.0322 (2188/68020). AF 95% confidence interval is 0.031. There are 62 homozygotes in gnomad4. There are 1782 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3557 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAFB2	NM_014649.3	c.1257C>T	p.Arg419=	synonymous_variant	9/21	ENST00000252542.9
SAFB2	XM_011528449.4	c.1257C>T	p.Arg419=	synonymous_variant	9/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAFB2	ENST00000252542.9	c.1257C>T	p.Arg419=	synonymous_variant	9/21	1	NM_014649.3	P1

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3557 AN: 152150 Hom.: 62 Cov.: 31

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0174

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0509

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0250 AC: 6276 AN: 251116 Hom.: 129 AF XY: 0.0256 AC XY: 3481 AN XY: 135780

Gnomad AFR exome AF: 0.00580

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.0357

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0160

Gnomad FIN exome AF: 0.0475

Gnomad NFE exome AF: 0.0322

Gnomad OTH exome AF: 0.0284

GnomAD4 exome AF: 0.0276 AC: 40392 AN: 1461784 Hom.: 681 Cov.: 31 AF XY: 0.0275 AC XY: 19972 AN XY: 727202

Gnomad4 AFR exome AF: 0.00433

Gnomad4 AMR exome AF: 0.0145

Gnomad4 ASJ exome AF: 0.0329

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.0478

Gnomad4 NFE exome AF: 0.0297

Gnomad4 OTH exome AF: 0.0256

GnomAD4 genome AF: 0.0234 AC: 3557 AN: 152268 Hom.: 62 Cov.: 31 AF XY: 0.0239 AC XY: 1782 AN XY: 74448

Gnomad4 AFR AF: 0.00614

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0509

Gnomad4 NFE AF: 0.0322

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0293 Hom.: 95

Bravo AF: 0.0199

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.0332

EpiControl AF: 0.0315

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.8
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs806706; hg19: chr19-5610045;