rs1849553

Positions:

• chr1-50852333-G-A

Variant summary

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

The NM_007051.3(FAF1):​c.114+5596C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,094 control chromosomes in the GnomAD database, including 4,444 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 (4444 hom., cov: 32)
• Consequence: FAF1 NM_007051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAF1	NM_007051.3	c.114+5596C>T		intron_variant		ENST00000396153.7
FAF1	XM_024452734.2	c.90+5596C>T		intron_variant
FAF1	XM_047442743.1	c.-148+5596C>T		intron_variant
FAF1	XM_047442745.1	c.-148+5596C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAF1	ENST00000396153.7	c.114+5596C>T		intron_variant		1	NM_007051.3	P1
FAF1	ENST00000487898.1	n.136+5596C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34864 AN: 151976 Hom.: 4442 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.229 AC: 34863 AN: 152094 Hom.: 4444 Cov.: 32 AF XY: 0.223 AC XY: 16615 AN XY: 74364

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.290

Alfa AF: 0.268 Hom.: 2465

Bravo AF: 0.230

Asia WGS AF: 0.124 AC: 429 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.84
DANN	Benign	0.67

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: rs1849553; hg19: chr1-51318005;