chr1-172665919-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000639.3(FASLG):c.749A>G(p.Asn250Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000608 in 1,612,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N250I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

FASLG
NM_000639.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Publications

2 publications found

Variant links:

Genes affected

FASLG (HGNC:11936): (Fas ligand) This gene is a member of the tumor necrosis factor superfamily. The primary function of the encoded transmembrane protein is the induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death. It has also been implicated in the progression of several cancers. Defects in this gene may be related to some cases of systemic lupus erythematosus (SLE). Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2014]

FASLG Gene-Disease associations (from GenCC):

autoimmune lymphoproliferative syndrome type 1
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
autoimmune lymphoproliferative syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FASLG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03513068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000639.3. 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
	FASLG	NM_000639.3	MANE Select	c.749A>G	p.Asn250Ser	missense	Exon 4 of 4	NP_000630.1	P48023-1
	FASLG	NM_001302746.2		c.*319A>G		3_prime_UTR	Exon 3 of 3	NP_001289675.1	P48023-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FASLG	ENST00000367721.3	TSL:1 MANE Select	c.749A>G	p.Asn250Ser	missense	Exon 4 of 4	ENSP00000356694.2	P48023-1
FASLG	ENST00000340030.4	TSL:1	c.*319A>G		3_prime_UTR	Exon 3 of 3	ENSP00000344739.3	P48023-2
FASLG	ENST00000875216.1		c.770A>G	p.Asn257Ser	missense	Exon 4 of 4	ENSP00000545275.1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

250988

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000466

AC:

AN:

1460414

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726220

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33418

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000576

AC:

AN:

1110836

Other (OTH)

AF:

0.0000497

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000197

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autoimmune lymphoproliferative syndrome type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

Eigen

Benign

-0.046

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.035

MetaSVM

Uncertain

0.042

MutationAssessor

Benign

1.2

PhyloP100

1.9

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.99

REVEL

Uncertain

0.42

Sift

Benign

0.066

Sift4G

Uncertain

0.0080

Polyphen

0.98

Vest4

0.14

MVP

0.88

MPC

0.49

ClinPred

0.59

GERP RS

1.8

Varity_R

0.18

gMVP

0.45

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over