19-5590333-C-G

Variant names:

• chr19-5590333-C-G
• rs140108933
• NM_014649.3:c.2470G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014649.3(SAFB2):​c.2470G>C​(p.Gly824Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SAFB2 NM_014649.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24846792).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAFB2	NM_014649.3	c.2470G>C	p.Gly824Arg	missense_variant	Exon 18 of 21	ENST00000252542.9	NP_055464.1
SAFB2	XM_011528449.4	c.2470G>C	p.Gly824Arg	missense_variant	Exon 18 of 21		XP_011526751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB2	ENST00000252542.9	c.2470G>C	p.Gly824Arg	missense_variant	Exon 18 of 21	1	NM_014649.3	ENSP00000252542.3
SAFB2	ENST00000589925.1	n.338G>C		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1457788 Hom.: 0 Cov.: 32 AF XY: 0.00000690 AC XY: 5 AN XY: 724888

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.080
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.47
MutPred		0.27		Gain of MoRF binding (P = 0.0343);
MVP		0.11
MPC		0.052
ClinPred		0.96	D
GERP RS		2.2
Varity_R		0.12
gMVP		0.097

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: rs140108933; hg19: chr19-5590344;