1-50491713-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007051.3(FAF1):c.1575+8T>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00223 in 1,599,036 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (27 hom.)
• Consequence: FAF1 NM_007051.3 splice_region, intron
• Scores: Splicing: ADA: 0.008688
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-50491713-A-C is Benign according to our data. Variant chr1-50491713-A-C is described in ClinVar as [Benign]. Clinvar id is 767670.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1746/152284) while in subpopulation AFR AF= 0.0385 (1599/41546). AF 95% confidence interval is 0.0369. There are 28 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1745 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAF1	NM_007051.3	c.1575+8T>G		splice_region_variant, intron_variant		ENST00000396153.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAF1	ENST00000396153.7	c.1575+8T>G		splice_region_variant, intron_variant		1	NM_007051.3	P1
FAF1	ENST00000494400.5	c.993+8T>G		splice_region_variant, intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1745 AN: 152166 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00319 AC: 773 AN: 242392 Hom.: 13 AF XY: 0.00254 AC XY: 332 AN XY: 130736

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.00362

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000362

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000224

Gnomad OTH exome AF: 0.00235

GnomAD4 exome AF: 0.00126 AC: 1822 AN: 1446752 Hom.: 27 Cov.: 29 AF XY: 0.00107 AC XY: 773 AN XY: 719606

Gnomad4 AFR exome AF: 0.0383

Gnomad4 AMR exome AF: 0.00236

Gnomad4 ASJ exome AF: 0.00288

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000240

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000203

Gnomad4 OTH exome AF: 0.00269

GnomAD4 genome AF: 0.0115 AC: 1746 AN: 152284 Hom.: 28 Cov.: 32 AF XY: 0.0113 AC XY: 842 AN XY: 74462

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00624 Hom.: 8

Bravo AF: 0.0134

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000329

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	11
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0087
dbscSNV1_RF	Benign	0.030
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: rs59743675; hg19: chr1-50957385;