1-50506892-G-A

Position:

• chr1-50506892-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.1495-15091C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,242 control chromosomes in the GnomAD database, including 62,350 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 0.90 (62350 hom., cov: 32)
• Consequence: FAF1 NM_007051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAF1	NM_007051.3	c.1495-15091C>T		intron_variant		ENST00000396153.7	NP_008982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAF1	ENST00000396153.7	c.1495-15091C>T		intron_variant		1	NM_007051.3	ENSP00000379457	P1
FAF1	ENST00000494400.5	c.913-15091C>T		intron_variant, NMD_transcript_variant		2		ENSP00000434929

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137309 AN: 152124 Hom.: 62274 Cov.: 32

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.903 AC: 137444 AN: 152242 Hom.: 62350 Cov.: 32 AF XY: 0.897 AC XY: 66738 AN XY: 74414

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.896

Alfa AF: 0.885 Hom.: 120911

Bravo AF: 0.919

Asia WGS AF: 0.811 AC: 2823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.27

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: rs1149795; hg19: chr1-50972564; COSMIC: COSV65637292;