rs722374

Positions:

• chr17-35419782-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018042.5(SLFN12):​c.1147+492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,018 control chromosomes in the GnomAD database, including 4,360 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 0.19 (4360 hom., cov: 32)
• Consequence: SLFN12 NM_018042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

Genes affected

SLFN12 (HGNC:25500): (schlafen family member 12) Predicted to act upstream of or within negative regulation of cell population proliferation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN12	NM_018042.5	c.1147+492C>T		intron_variant		ENST00000304905.10
SLFN12	NM_001289009.2	c.1147+492C>T		intron_variant
SLFN12	XM_005257995.6	c.1147+492C>T		intron_variant
SLFN12	XM_024450822.2	c.1147+492C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN12	ENST00000304905.10	c.1147+492C>T		intron_variant		1	NM_018042.5	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29484 AN: 151900 Hom.: 4353 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29537 AN: 152018 Hom.: 4360 Cov.: 32 AF XY: 0.195 AC XY: 14506 AN XY: 74322

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0884

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.0530

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.180

Alfa AF: 0.124 Hom.: 1484

Bravo AF: 0.209

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs722374; hg19: chr17-33746801;