Variant 1-50491713-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.44

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 1746 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAF1	NM_007051.3 linkuse as main transcript	c.1575+8T>G		splice_region_variant, intron_variant		ENST00000396153.7	NP_008982.1	Q9UNN5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAF1	ENST00000396153.7 linkuse as main transcript	c.1575+8T>G		splice_region_variant, intron_variant		1	NM_007051.3	ENSP00000379457.2		Q9UNN5-1
FAF1	ENST00000494400.5 linkuse as main transcript	n.993+8T>G		splice_region_variant, intron_variant		2		ENSP00000434929.1		B3KT28

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1745

AN:

152166

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00254

AC XY:

332

AN XY:

130736

show subpopulations

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.:

Cov.:

AF XY:

0.00107

AC XY:

773

AN XY:

719606

show subpopulations

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.:

Cov.:

AF XY:

0.0113

AC XY:

842

AN XY:

74462

show subpopulations

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.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000329

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over