1-50472176-T-C

Position:

• chr1-50472176-T-C

Variant summary

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

The NM_007051.3(FAF1):​c.1869+3288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,588 control chromosomes in the GnomAD database, including 8,886 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 0.30 (8886 hom., cov: 30)
• Consequence: FAF1 NM_007051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAF1	NM_007051.3	c.1869+3288A>G		intron_variant		ENST00000396153.7	NP_008982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAF1	ENST00000396153.7	c.1869+3288A>G		intron_variant		1	NM_007051.3	ENSP00000379457	P1
FAF1	ENST00000494400.5	c.1287+3288A>G		intron_variant, NMD_transcript_variant		2		ENSP00000434929

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45969 AN: 151470 Hom.: 8874 Cov.: 30

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.303 AC: 45987 AN: 151588 Hom.: 8886 Cov.: 30 AF XY: 0.317 AC XY: 23444 AN XY: 74024

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.282

Alfa AF: 0.316 Hom.: 17580

Bravo AF: 0.298

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.53

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: rs3827730; hg19: chr1-50937848; COSMIC: COSV65637285; COSMIC: COSV65637285;