1-50807685-C-G

Position:

• chr1-50807685-C-G

Variant summary

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

The NM_007051.3(FAF1):​c.115-6008G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,990 control chromosomes in the GnomAD database, including 7,607 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 0.31 (7607 hom., cov: 31)
• Consequence: FAF1 NM_007051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAF1	NM_007051.3	c.115-6008G>C		intron_variant		ENST00000396153.7
FAF1	XM_024452734.2	c.91-6008G>C		intron_variant
FAF1	XM_047442743.1	c.-147-6008G>C		intron_variant
FAF1	XM_047442745.1	c.-147-6008G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAF1	ENST00000396153.7	c.115-6008G>C		intron_variant		1	NM_007051.3	P1
FAF1	ENST00000487898.1	n.137-6008G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47069 AN: 151872 Hom.: 7595 Cov.: 31

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.0757

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.310 AC: 47109 AN: 151990 Hom.: 7607 Cov.: 31 AF XY: 0.304 AC XY: 22576 AN XY: 74300

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.0757

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.361

Alfa AF: 0.156 Hom.: 272

Bravo AF: 0.315

Asia WGS AF: 0.191 AC: 662 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	0.94
DANN	Benign	0.30

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: rs6588392; hg19: chr1-51273357;