Genetic Variant SLFN11:c.1070-26G>A (chr17-35360397-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001376007.1(SLFN11):c.1070-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,586,064 control chromosomes in the GnomAD database, including 66,354 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 0.37 ( 12499 hom., cov: 29)

Exomes 𝑓: 0.26 ( 53855 hom. )

Consequence

SLFN11
NM_001376007.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0760

Publications

11 publications found

Variant links:

Genes affected

SLFN11 (HGNC:26633): (schlafen family member 11) Enables tRNA binding activity. Involved in several processes, including defense response to virus; negative regulation of G1/S transition of mitotic cell cycle; and replication fork arrest. Located in cytosol; nucleoplasm; and site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]

SLFN11 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN11	NM_001376007.1 link	c.1070-26G>A		intron_variant	Intron 4 of 6	ENST00000685675.1	NP_001362936.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLFN11	ENST00000685675.1 link	c.1070-26G>A	intron_variant	Intron 4 of 6		NM_001376007.1	ENSP00000510787.1
SLFN11	ENST00000308377.8 link	c.1070-26G>A	intron_variant	Intron 2 of 4	1		ENSP00000312402.4
SLFN11	ENST00000394566.5 link	c.1070-26G>A	intron_variant	Intron 4 of 6	2		ENSP00000378067.1
SLFN11	ENST00000586099.1 link	n.227-26G>A	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

55595

AN:

150480

Hom.:

12477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.330

GnomAD2 exomes

AF:

0.320

AC:

74170

AN:

231654

AF XY:

0.306

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.494

Gnomad FIN exome

AF:

0.290

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.258

AC:

370171

AN:

1435464

Hom.:

53855

Cov.:

AF XY:

0.257

AC XY:

183750

AN XY:

713704

show subpopulations

African (AFR)

AF:

0.627

AC:

19848

AN:

31650

American (AMR)

AF:

0.446

AC:

17295

AN:

38780

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

5117

AN:

25236

East Asian (EAS)

AF:

0.492

AC:

19287

AN:

39206

South Asian (SAS)

AF:

0.329

AC:

26819

AN:

81568

European-Finnish (FIN)

AF:

0.289

AC:

15226

AN:

52686

Middle Eastern (MID)

AF:

0.251

AC:

1426

AN:

5692

European-Non Finnish (NFE)

AF:

0.225

AC:

248267

AN:

1101252

Other (OTH)

AF:

0.284

AC:

16886

AN:

59394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

11558

23116

34673

46231

57789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8926

17852

26778

35704

44630

<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:

0.370

AC:

55664

AN:

150600

Hom.:

12499

Cov.:

AF XY:

0.374

AC XY:

27445

AN XY:

73438

show subpopulations

African (AFR)

AF:

0.617

AC:

25284

AN:

40994

American (AMR)

AF:

0.396

AC:

5952

AN:

15044

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

749

AN:

3458

East Asian (EAS)

AF:

0.479

AC:

2448

AN:

5106

South Asian (SAS)

AF:

0.343

AC:

1631

AN:

4758

European-Finnish (FIN)

AF:

0.297

AC:

3035

AN:

10216

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15426

AN:

67732

Other (OTH)

AF:

0.332

AC:

694

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1505

3009

4514

6018

7523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.272

Hom.:

29314

Bravo

AF:

0.389

Asia WGS

AF:

0.436

AC:

1515

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.1

(source)

DANN

Benign

0.75

PhyloP100

-0.076

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