rs2285963

chr19-5591724-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014649.3(SAFB2):c.2394+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,608,754 control chromosomes in the GnomAD database, including 16,242 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 0.14 (1478 hom., cov: 31)
  • Exomes 𝑓: 0.14 (14764 hom.)
• Consequence: SAFB2 NM_014649.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAFB2	NM_014649.3	c.2394+24C>T		intron_variant		ENST00000252542.9
SAFB2	XM_011528449.4	c.2394+24C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAFB2	ENST00000252542.9	c.2394+24C>T		intron_variant		1	NM_014649.3	P1
SAFB2	ENST00000590000.1	n.205C>T		non_coding_transcript_exon_variant	2/2	2
SAFB2	ENST00000589925.1	n.262+24C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20650 AN: 151818 Hom.: 1479 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.0999

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.144 AC: 36011 AN: 250888 Hom.: 2811 AF XY: 0.151 AC XY: 20415 AN XY: 135622

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.247

Gnomad FIN exome AF: 0.0987

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.137 AC: 200054 AN: 1456818 Hom.: 14764 Cov.: 29 AF XY: 0.141 AC XY: 102162 AN XY: 725016

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.136 AC: 20658 AN: 151936 Hom.: 1478 Cov.: 31 AF XY: 0.137 AC XY: 10153 AN XY: 74256

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.0999

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.120

Alfa AF: 0.130 Hom.: 1923

Bravo AF: 0.134

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.4
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2285963; hg19: chr19-5591735; COSMIC: COSV53040887; COSMIC: COSV53040887;