17-35490403-A-G

Variant names:

• chr17-35490403-A-G
• rs9909601
• NM_001363830.2:c.87-10208T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363830.2(SLFN12L):​c.87-10208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,256,114 control chromosomes in the GnomAD database, including 329,467 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 (41320 hom., cov: 32)
  • Exomes 𝑓: 0.72 (288147 hom.)
• Consequence: SLFN12L NM_001363830.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 10 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363830.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN12L	NM_001363830.2	MANE Select	c.87-10208T>C		intron	N/A	NP_001350759.2
	SLFN12L	NM_001195790.3		c.-287-2431T>C		intron	N/A	NP_001182719.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN12L	ENST00000628453.4	TSL:5 MANE Select	c.87-10208T>C		intron	N/A	ENSP00000487397.4
	E2F3P1	ENST00000589887.1	TSL:6	n.395A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111273 AN: 152000 Hom.: 41282 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.735

GnomAD4 exome AF: 0.724 AC: 799709 AN: 1103996 Hom.: 288147 Cov.: 22 AF XY: 0.723 AC XY: 407881 AN XY: 564166

African (AFR) AF: 0.877 AC: 24335 AN: 27738

American (AMR) AF: 0.700 AC: 30848 AN: 44052

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 18019 AN: 24018

East Asian (EAS) AF: 0.725 AC: 27509 AN: 37926

South Asian (SAS) AF: 0.750 AC: 59603 AN: 79486

European-Finnish (FIN) AF: 0.634 AC: 33061 AN: 52130

Middle Eastern (MID) AF: 0.774 AC: 3987 AN: 5154

European-Non Finnish (NFE) AF: 0.723 AC: 567226 AN: 785014

Other (OTH) AF: 0.724 AC: 35121 AN: 48478

GnomAD4 genome AF: 0.732 AC: 111372 AN: 152118 Hom.: 41320 Cov.: 32 AF XY: 0.728 AC XY: 54158 AN XY: 74342

African (AFR) AF: 0.865 AC: 35932 AN: 41520

American (AMR) AF: 0.699 AC: 10691 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3472

East Asian (EAS) AF: 0.667 AC: 3442 AN: 5160

South Asian (SAS) AF: 0.759 AC: 3655 AN: 4816

European-Finnish (FIN) AF: 0.630 AC: 6653 AN: 10568

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46074 AN: 67978

Other (OTH) AF: 0.736 AC: 1554 AN: 2112

Alfa AF: 0.761 Hom.: 11025

Bravo AF: 0.743

Asia WGS AF: 0.725 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9909601; hg19: chr17-33817422;