dbSNP rs5030772: FASLG:c.395-124A>G (chr1-172664210-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000639.3(FASLG):c.395-124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 954,906 control chromosomes in the GnomAD database, including 8,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.099 ( 1080 hom., cov: 32)

Exomes 𝑓: 0.13 ( 7337 hom. )

Consequence

FASLG
NM_000639.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.181

Publications

51 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: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-172664210-A-G is Benign according to our data. Variant chr1-172664210-A-G is described in ClinVar as Benign. ClinVar VariationId is 1273293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASLG	NM_000639.3 link	c.395-124A>G		intron_variant	Intron 2 of 3	ENST00000367721.3	NP_000630.1
FASLG	NM_001302746.2 link	c.349-124A>G		intron_variant	Intron 1 of 2		NP_001289675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASLG	ENST00000367721.3 link	c.395-124A>G		intron_variant	Intron 2 of 3	1	NM_000639.3	ENSP00000356694.2
FASLG	ENST00000340030.4 link	c.349-124A>G		intron_variant	Intron 1 of 2	1		ENSP00000344739.3

Frequencies

GnomAD3 genomes

AF:

0.0991

AC:

15081

AN:

152130

Hom.:

1079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.0983

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0940

Gnomad FIN

AF:

0.0841

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.127

AC:

101683

AN:

802658

Hom.:

7337

AF XY:

0.127

AC XY:

53106

AN XY:

417166

show subpopulations

African (AFR)

AF:

0.0234

AC:

455

AN:

19464

American (AMR)

AF:

0.0709

AC:

2362

AN:

33304

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

3780

AN:

20638

East Asian (EAS)

AF:

0.000248

AC:

AN:

32298

South Asian (SAS)

AF:

0.110

AC:

7170

AN:

65336

European-Finnish (FIN)

AF:

0.0926

AC:

4341

AN:

46892

Middle Eastern (MID)

AF:

0.139

AC:

393

AN:

2828

European-Non Finnish (NFE)

AF:

0.144

AC:

78470

AN:

544302

Other (OTH)

AF:

0.125

AC:

4704

AN:

37596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4464

8928

13391

17855

22319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1840

3680

5520

7360

9200

<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:

0.0991

AC:

15081

AN:

152248

Hom.:

1080

Cov.:

AF XY:

0.0958

AC XY:

7132

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0251

AC:

1045

AN:

41572

American (AMR)

AF:

0.0981

AC:

1501

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

649

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5190

South Asian (SAS)

AF:

0.0943

AC:

455

AN:

4824

European-Finnish (FIN)

AF:

0.0841

AC:

892

AN:

10602

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10103

AN:

67982

Other (OTH)

AF:

0.115

AC:

243

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

667

1334

2000

2667

3334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.117

Hom.:

141

Bravo

AF:

0.0976

Asia WGS

AF:

0.0420

AC:

146

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.9

(source)

DANN

Benign

0.43

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over