1-50708658-C-T

Position:

• chr1-50708658-C-T

Variant summary

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

The NM_007051.3(FAF1):​c.552-2767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,716 control chromosomes in the GnomAD database, including 8,945 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 (8945 hom., cov: 31)
• Consequence: FAF1 NM_007051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAF1	NM_007051.3	c.552-2767G>A		intron_variant		ENST00000396153.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAF1	ENST00000396153.7	c.552-2767G>A		intron_variant		1	NM_007051.3	P1
FAF1	ENST00000487898.1	n.574-2767G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44812 AN: 151598 Hom.: 8932 Cov.: 31

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.295 AC: 44827 AN: 151716 Hom.: 8945 Cov.: 31 AF XY: 0.308 AC XY: 22818 AN XY: 74100

Gnomad4 AFR AF: 0.0696

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.285

Alfa AF: 0.325 Hom.: 15120

Bravo AF: 0.289

Asia WGS AF: 0.460 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.46

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: rs11205760; hg19: chr1-51174330;