rs17387761

chr1-50612417-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_007051.3(FAF1):c.745-16201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,159,192 control chromosomes in the GnomAD database, including 43,174 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 0.23 (4496 hom., cov: 32)
  • Exomes 𝑓: 0.28 (38678 hom.)
• Consequence: FAF1 NM_007051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719

Genes affected

FAF1 (HGNC:3578): (Fas associated factor 1) Interaction of Fas ligand (TNFSF6) with the FAS antigen (TNFRSF6) mediates programmed cell death, also called apoptosis, in a number of organ systems. The protein encoded by this gene binds to FAS antigen and can initiate apoptosis or enhance apoptosis initiated through FAS antigen. Initiation of apoptosis by the protein encoded by this gene requires a ubiquitin-like domain but not the FAS-binding domain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAF1	NM_007051.3	c.745-16201C>T		intron_variant		ENST00000396153.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAF1	ENST00000396153.7	c.745-16201C>T		intron_variant		1	NM_007051.3	P1
FAF1	ENST00000494400.5	c.163-16201C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35213 AN: 152036 Hom.: 4494 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.275 AC: 277207 AN: 1007038 Hom.: 38678 Cov.: 18 AF XY: 0.275 AC XY: 134283 AN XY: 487526

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.00227

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.231 AC: 35213 AN: 152154 Hom.: 4496 Cov.: 32 AF XY: 0.226 AC XY: 16800 AN XY: 74384

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.290

Alfa AF: 0.231 Hom.: 669

Bravo AF: 0.233

Asia WGS AF: 0.123 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	15
Dann	Benign	0.87

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: rs17387761; hg19: chr1-51078089; COSMIC: COSV65635835;