rs17382596

Variant names:

• chr1-50472787-T-G
• rs17382596
• NM_007051.3:c.1869+2677A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_007051.3(FAF1):​c.1869+2677A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,144 control chromosomes in the GnomAD database, including 5,307 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 0.25 (5307 hom., cov: 32)
• Consequence: FAF1 NM_007051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAF1	NM_007051.3	c.1869+2677A>C		intron_variant	Intron 18 of 18	ENST00000396153.7	NP_008982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAF1	ENST00000396153.7	c.1869+2677A>C		intron_variant	Intron 18 of 18	1	NM_007051.3	ENSP00000379457.2
FAF1	ENST00000494400.5	n.1287+2677A>C		intron_variant	Intron 12 of 13	2		ENSP00000434929.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38241 AN: 152026 Hom.: 5305 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.251 AC: 38239 AN: 152144 Hom.: 5307 Cov.: 32 AF XY: 0.245 AC XY: 18211 AN XY: 74360

African (AFR) AF: 0.183 AC: 7604 AN: 41504

American (AMR) AF: 0.247 AC: 3772 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3466

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5192

South Asian (SAS) AF: 0.238 AC: 1147 AN: 4826

European-Finnish (FIN) AF: 0.211 AC: 2233 AN: 10594

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21078 AN: 67970

Other (OTH) AF: 0.303 AC: 640 AN: 2110

Alfa AF: 0.275 Hom.: 3328

Bravo AF: 0.251

Asia WGS AF: 0.126 AC: 436 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17382596; hg19: chr1-50938459;