Genetic Variant SAFB2:c.2394+24C>T (chr19-5591724-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0340

Publications

8 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 -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 rank	MANE	Protein	UniProt
SAFB2	NM_014649.3 link	c.2394+24C>T		intron_variant	Intron 17 of 20	ENST00000252542.9	NP_055464.1	Q14151-1
SAFB2	XM_011528449.4 link	c.2394+24C>T		intron_variant	Intron 17 of 20		XP_011526751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAFB2	ENST00000252542.9 link	c.2394+24C>T		intron_variant	Intron 17 of 20	1	NM_014649.3	ENSP00000252542.3		Q14151-1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20650

AN:

151818

Hom.:

1479

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.144

AC:

36011

AN:

250888

AF XY:

0.151

show subpopulations

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 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.:

AF XY:

0.141

AC XY:

102162

AN XY:

725016

show subpopulations

African (AFR)

AF:

0.145

AC:

4850

AN:

33378

American (AMR)

AF:

0.114

AC:

5098

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

3370

AN:

26114

East Asian (EAS)

AF:

0.218

AC:

8655

AN:

39654

South Asian (SAS)

AF:

0.243

AC:

20916

AN:

86114

European-Finnish (FIN)

AF:

0.103

AC:

5471

AN:

53324

Middle Eastern (MID)

AF:

0.146

AC:

840

AN:

5758

European-Non Finnish (NFE)

AF:

0.129

AC:

142393

AN:

1107584

Other (OTH)

AF:

0.141

AC:

8461

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

7458

14916

22374

29832

37290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5382

10764

16146

21528

26910

<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:

0.136

AC:

20658

AN:

151936

Hom.:

1478

Cov.:

AF XY:

0.137

AC XY:

10153

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.148

AC:

6133

AN:

41420

American (AMR)

AF:

0.130

AC:

1979

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

431

AN:

3468

East Asian (EAS)

AF:

0.175

AC:

903

AN:

5160

South Asian (SAS)

AF:

0.237

AC:

1137

AN:

4796

European-Finnish (FIN)

AF:

0.0999

AC:

1056

AN:

10574

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8611

AN:

67960

Other (OTH)

AF:

0.120

AC:

252

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

892

1785

2677

3570

4462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.130

Hom.:

2591

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

(source)

DANN

Benign

0.86

PhyloP100

-0.034

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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