Genetic Variant NM_001363830.2:c.87-10916C>T (chr17-35491111-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_001363830.2(SLFN12L):c.87-10916C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 773,562 control chromosomes in the GnomAD database, including 85,683 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 0.49 ( 18628 hom., cov: 32)

Exomes 𝑓: 0.45 ( 67055 hom. )

Consequence

SLFN12L
NM_001363830.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.53

Publications

8 publications found

Variant links:

Genes affected

SLFN12L (HGNC:33920): (schlafen family member 12 like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLFN12L links:

E2F3P1 (HGNC:3116): (E2F transcription factor 3 pseudogene 1)

E2F3P1 links:

Genome browser will be placed here

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 (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLFN12L	NM_001363830.2 link	c.87-10916C>T	intron_variant	Intron 2 of 4	ENST00000628453.4	NP_001350759.2
E2F3P1		n.35491111G>A	intragenic_variant
SLFN12L	NM_001195790.3 link	c.-287-3139C>T	intron_variant	Intron 2 of 5		NP_001182719.2	Q6IEE8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN12L	ENST00000628453.4 link	c.87-10916C>T		intron_variant	Intron 2 of 4	5	NM_001363830.2	ENSP00000487397.4		A0A8I5QCZ1
E2F3P1	ENST00000589887.1 link	n.1103G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.490

AC:

74467

AN:

151898

Hom.:

18625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.502

GnomAD4 exome

AF:

0.454

AC:

282369

AN:

621548

Hom.:

67055

Cov.:

AF XY:

0.449

AC XY:

151683

AN XY:

337526

show subpopulations

African (AFR)

AF:

0.559

AC:

9691

AN:

17332

American (AMR)

AF:

0.419

AC:

17390

AN:

41472

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

10294

AN:

19794

East Asian (EAS)

AF:

0.292

AC:

10438

AN:

35780

South Asian (SAS)

AF:

0.304

AC:

20570

AN:

67738

European-Finnish (FIN)

AF:

0.404

AC:

20657

AN:

51192

Middle Eastern (MID)

AF:

0.470

AC:

1902

AN:

4050

European-Non Finnish (NFE)

AF:

0.501

AC:

176151

AN:

351742

Other (OTH)

AF:

0.471

AC:

15276

AN:

32448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

7642

15285

22927

30570

38212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1128

2256

3384

4512

5640

<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:

0.490

AC:

74500

AN:

152014

Hom.:

18628

Cov.:

AF XY:

0.479

AC XY:

35556

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.555

AC:

23011

AN:

41440

American (AMR)

AF:

0.446

AC:

6818

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1815

AN:

3466

East Asian (EAS)

AF:

0.284

AC:

1468

AN:

5166

South Asian (SAS)

AF:

0.298

AC:

1437

AN:

4816

European-Finnish (FIN)

AF:

0.398

AC:

4207

AN:

10574

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.502

AC:

34109

AN:

67950

Other (OTH)

AF:

0.501

AC:

1057

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1931

3861

5792

7722

9653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<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:

0.493

Hom.:

17343

Bravo

AF:

0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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