10-88991759-C-T

Variant names:

• chr10-88991759-C-T
• rs1324551
• NM_000043.6:c.30+853C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000043.6(FAS):​c.30+853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,954 control chromosomes in the GnomAD database, including 26,311 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 0.57 (26301 hom., cov: 31)
  • Exomes 𝑓: 0.64 (10 hom.)
• Consequence: FAS NM_000043.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 31 publications found

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]

ENSG00000286116 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAS	NM_000043.6	MANE Select	c.30+853C>T		intron	N/A	NP_000034.1
	FAS	NM_001410956.1		c.75+547C>T		intron	N/A	NP_001397885.1
	FAS	NM_152871.4		c.30+853C>T		intron	N/A	NP_690610.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAS	ENST00000652046.1	MANE Select	c.30+853C>T		intron	N/A	ENSP00000498466.1
	FAS	ENST00000357339.7	TSL:1	c.30+853C>T		intron	N/A	ENSP00000349896.2
	FAS	ENST00000355279.2	TSL:1	c.30+853C>T		intron	N/A	ENSP00000347426.2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86978 AN: 151792 Hom.: 26244 Cov.: 31

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.636 AC: 28 AN: 44 Hom.: 10 AF XY: 0.647 AC XY: 22 AN XY: 34

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 21 AN: 30

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.573 AC: 87101 AN: 151910 Hom.: 26301 Cov.: 31 AF XY: 0.570 AC XY: 42278 AN XY: 74232

African (AFR) AF: 0.777 AC: 32213 AN: 41440

American (AMR) AF: 0.551 AC: 8419 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1497 AN: 3466

East Asian (EAS) AF: 0.474 AC: 2441 AN: 5150

South Asian (SAS) AF: 0.444 AC: 2140 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4934 AN: 10534

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33705 AN: 67926

Other (OTH) AF: 0.553 AC: 1166 AN: 2108

Alfa AF: 0.550 Hom.: 7483

Bravo AF: 0.589

Asia WGS AF: 0.543 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.1
DANN	Benign	0.78
PhyloP100		-0.21
PromoterAI		0.038	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1324551; hg19: chr10-90751516;