19-5595343-T-C

Variant names:

• chr19-5595343-T-C
• rs10413286
• NM_014649.3:c.1919+18A>G

Variant summary

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

The NM_014649.3(SAFB2):​c.1919+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,604,700 control chromosomes in the GnomAD database, including 378,938 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 0.73 (41628 hom., cov: 30)
  • Exomes 𝑓: 0.68 (337310 hom.)
• Consequence: SAFB2 NM_014649.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAFB2	NM_014649.3	c.1919+18A>G		intron_variant	Intron 14 of 20	ENST00000252542.9	NP_055464.1
SAFB2	XM_011528449.4	c.1919+18A>G		intron_variant	Intron 14 of 20		XP_011526751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB2	ENST00000252542.9	c.1919+18A>G		intron_variant	Intron 14 of 20	1	NM_014649.3	ENSP00000252542.3

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111341 AN: 151850 Hom.: 41584 Cov.: 30

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.727

GnomAD3 exomes AF: 0.732 AC: 179927 AN: 245918 Hom.: 66842 AF XY: 0.729 AC XY: 97268 AN XY: 133400

Gnomad AFR exome AF: 0.867

Gnomad AMR exome AF: 0.793

Gnomad ASJ exome AF: 0.755

Gnomad EAS exome AF: 0.891

Gnomad SAS exome AF: 0.816

Gnomad FIN exome AF: 0.648

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.715

GnomAD4 exome AF: 0.678 AC: 984635 AN: 1452732 Hom.: 337310 Cov.: 48 AF XY: 0.681 AC XY: 492417 AN XY: 723002

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.786

Gnomad4 ASJ exome AF: 0.754

Gnomad4 EAS exome AF: 0.884

Gnomad4 SAS exome AF: 0.812

Gnomad4 FIN exome AF: 0.655

Gnomad4 NFE exome AF: 0.647

Gnomad4 OTH exome AF: 0.703

GnomAD4 genome AF: 0.733 AC: 111447 AN: 151968 Hom.: 41628 Cov.: 30 AF XY: 0.734 AC XY: 54492 AN XY: 74258

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.730

Alfa AF: 0.677 Hom.: 28437

Bravo AF: 0.744

Asia WGS AF: 0.849 AC: 2952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.28

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: rs10413286; hg19: chr19-5595354;