chr1-50441487-C-T

Variant names:

• chr1-50441487-C-T
• NM_007051.3:c.1906G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007051.3(FAF1):​c.1906G>A​(p.Val636Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,393,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAF1 NM_007051.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76
• Publications: 0 publications found

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]

FAF1-AS1 (HGNC:40228): (FAF1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21944949).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007051.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAF1	NM_007051.3	MANE Select	c.1906G>A	p.Val636Ile	missense	Exon 19 of 19	NP_008982.1	Q9UNN5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAF1	ENST00000396153.7	TSL:1 MANE Select	c.1906G>A	p.Val636Ile	missense	Exon 19 of 19	ENSP00000379457.2	Q9UNN5-1
	FAF1	ENST00000952059.1		c.2002G>A	p.Val668Ile	missense	Exon 20 of 20	ENSP00000622118.1
	FAF1	ENST00000952061.1		c.1966G>A	p.Val656Ile	missense	Exon 20 of 20	ENSP00000622120.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1393764 Hom.: 0 Cov.: 28 AF XY: 0.00000146 AC XY: 1 AN XY: 686512

African (AFR) AF: 0.00 AC: 0 AN: 31496

American (AMR) AF: 0.00 AC: 0 AN: 35452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25088

East Asian (EAS) AF: 0.00 AC: 0 AN: 35640

South Asian (SAS) AF: 0.00 AC: 0 AN: 78780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49236

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5666

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074642

Other (OTH) AF: 0.00 AC: 0 AN: 57764

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.0012
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.18	N
PhyloP100		3.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.10
Sift	Uncertain	0.029	D
Sift4G	Benign	0.14	T
Polyphen		0.011	B
Vest4		0.26
MutPred		0.49		Loss of methylation at K637 (P = 0.0545)
MVP		0.40
MPC		1.0
ClinPred		0.55	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.34
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-50907159;