10-88991583-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000043.6(FAS):c.30+677A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 154,376 control chromosomes in the GnomAD database, including 9,032 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 0.33 ( 8885 hom., cov: 33)

Exomes 𝑓: 0.35 ( 147 hom. )

Consequence

FAS
NM_000043.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

29 publications found

Variant links:

Genes affected

FAS (HGNC:11920): (Fas cell surface death receptor) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. [provided by RefSeq, Mar 2011]

FAS links:

ENSG00000286116 (HGNC:):

ENSG00000286116 links:

FAS-AS1 (HGNC:37128): (FAS antisense RNA 1)

FAS-AS1 links:

ACTA2 (HGNC:130): (actin alpha 2, smooth muscle) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a smooth muscle actin that is involved in vascular contractility and blood pressure homeostasis. Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, and Moyamoya disease, as well as multisystemic smooth muscle dysfunction syndrome. [provided by RefSeq, Sep 2017]

ACTA2 Gene-Disease associations (from GenCC):

multisystemic smooth muscle dysfunction syndrome
Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
aortic aneurysm, familial thoracic 6
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Moyamoya disease 5
Inheritance: AD Classification: STRONG Submitted by: G2P, Genomics England PanelApp
connective tissue disorder
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACTA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000043.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAS	NM_000043.6	MANE Select	c.30+677A>G	intron	N/A	NP_000034.1	P25445-1
FAS	NM_001410956.1		c.75+371A>G	intron	N/A	NP_001397885.1	A0A8Q3SIR6
FAS	NM_152871.4		c.30+677A>G	intron	N/A	NP_690610.1	P25445-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAS	ENST00000652046.1	MANE Select	c.30+677A>G	intron	N/A	ENSP00000498466.1	P25445-1
FAS	ENST00000357339.7	TSL:1	c.30+677A>G	intron	N/A	ENSP00000349896.2	P25445-6
FAS	ENST00000355279.2	TSL:1	c.30+677A>G	intron	N/A	ENSP00000347426.2	P25445-7

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

50075

AN:

152056

Hom.:

8885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.349

GnomAD4 exome

AF:

0.348

AC:

765

AN:

2200

Hom.:

147

Cov.:

AF XY:

0.366

AC XY:

427

AN XY:

1168

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AF:

0.301

AC:

103

AN:

342

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

AN:

East Asian (EAS)

AF:

0.660

AC:

AN:

South Asian (SAS)

AF:

0.447

AC:

134

AN:

300

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.329

AC:

450

AN:

1368

Other (OTH)

AF:

0.325

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.329

AC:

50079

AN:

152176

Hom.:

8885

Cov.:

AF XY:

0.334

AC XY:

24845

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.197

AC:

8164

AN:

41542

American (AMR)

AF:

0.353

AC:

5401

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1502

AN:

3466

East Asian (EAS)

AF:

0.521

AC:

2694

AN:

5172

South Asian (SAS)

AF:

0.443

AC:

2127

AN:

4806

European-Finnish (FIN)

AF:

0.381

AC:

4034

AN:

10592

Middle Eastern (MID)

AF:

0.370

AC:

108

AN:

292

European-Non Finnish (NFE)

AF:

0.367

AC:

24934

AN:

67986

Other (OTH)

AF:

0.347

AC:

733

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1764

3528

5291

7055

8819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.339

Hom.:

5828

Bravo

AF:

0.320

Asia WGS

AF:

0.407

AC:

1414

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

1.1

PromoterAI

0.084

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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