Genetic Variant SAFB2:p.Arg419Arg (chr19-5610034-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_014649.3(SAFB2):c.1257C>T(p.Arg419Arg) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.364

Publications

6 publications found

Variant links:

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]

SAFB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 3557 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAFB2	NM_014649.3 link	c.1257C>T	p.Arg419Arg	synonymous_variant	Exon 9 of 21	ENST00000252542.9	NP_055464.1	Q14151-1
SAFB2	XM_011528449.4 link	c.1257C>T	p.Arg419Arg	synonymous_variant	Exon 9 of 21		XP_011526751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB2	ENST00000252542.9 link	c.1257C>T	p.Arg419Arg	synonymous_variant	Exon 9 of 21	1	NM_014649.3	ENSP00000252542.3		Q14151-1

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3557

AN:

152150

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0250

AC:

6276

AN:

251116

AF XY:

0.0256

show subpopulations

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 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.:

AF XY:

0.0275

AC XY:

19972

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.00433

AC:

145

AN:

33480

American (AMR)

AF:

0.0145

AC:

650

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

860

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0161

AC:

1386

AN:

86252

European-Finnish (FIN)

AF:

0.0478

AC:

2551

AN:

53396

Middle Eastern (MID)

AF:

0.0321

AC:

185

AN:

5768

European-Non Finnish (NFE)

AF:

0.0297

AC:

33067

AN:

1111936

Other (OTH)

AF:

0.0256

AC:

1546

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

1982

3964

5946

7928

9910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1158

2316

3474

4632

5790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0234

AC:

3557

AN:

152268

Hom.:

Cov.:

AF XY:

0.0239

AC XY:

1782

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00614

AC:

255

AN:

41550

American (AMR)

AF:

0.0174

AC:

266

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

131

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.0133

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0509

AC:

540

AN:

10608

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0322

AC:

2188

AN:

68020

Other (OTH)

AF:

0.0260

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

174

349

523

698

872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0284

Hom.:

114

Bravo

AF:

0.0199

Asia WGS

AF:

0.00577

AC:

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

(source)

DANN

Benign

0.75

PhyloP100

0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over