chr19-5595343-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014649.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAFB2	NM_014649.3	MANE Select	c.1919+18A>G		intron	N/A	NP_055464.1	Q14151-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAFB2	ENST00000252542.9	TSL:1 MANE Select	c.1919+18A>G		intron	N/A	ENSP00000252542.3	Q14151-1
	SAFB2	ENST00000912090.1		c.1919+18A>G		intron	N/A	ENSP00000582149.1
	SAFB2	ENST00000850599.1		c.1919+18A>G		intron	N/A	ENSP00000520886.1	Q14151-1

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

GnomAD2 exomes AF: 0.732 AC: 179927 AN: 245918 AF XY: 0.729

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 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

African (AFR) AF: 0.875 AC: 29182 AN: 33362

American (AMR) AF: 0.786 AC: 35017 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 19660 AN: 26082

East Asian (EAS) AF: 0.884 AC: 35055 AN: 39672

South Asian (SAS) AF: 0.812 AC: 69934 AN: 86134

European-Finnish (FIN) AF: 0.655 AC: 30499 AN: 46542

Middle Eastern (MID) AF: 0.738 AC: 3639 AN: 4934

European-Non Finnish (NFE) AF: 0.647 AC: 719334 AN: 1111254

Other (OTH) AF: 0.703 AC: 42315 AN: 60198

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

African (AFR) AF: 0.858 AC: 35567 AN: 41474

American (AMR) AF: 0.753 AC: 11507 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2635 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4582 AN: 5150

South Asian (SAS) AF: 0.814 AC: 3911 AN: 4802

European-Finnish (FIN) AF: 0.652 AC: 6883 AN: 10558

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44062 AN: 67930

Other (OTH) AF: 0.730 AC: 1535 AN: 2102

Alfa AF: 0.682 Hom.: 37918

Bravo AF: 0.744

Asia WGS AF: 0.849 AC: 2952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.28
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10413286; hg19: chr19-5595354;