rs9288318

Variant names:

• chr2-201331340-C-A
• rs9288318
• NM_001127391.3:c.525-507G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-201331340-C-A
• chr2-201331340-C-G
• chr2-201331340-C-T

Variant summary

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

The NM_001127391.3(FLACC1):​c.525-507G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,832 control chromosomes in the GnomAD database, including 31,085 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 0.63 (31085 hom., cov: 30)
• Consequence: FLACC1 NM_001127391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 8 publications found

Genes affected

FLACC1 (HGNC:14439): (flagellum associated containing coiled-coil domains 1) Predicted to be located in cytoplasmic vesicle and sperm flagellum. Predicted to be active in cytoplasm; outer dense fiber; and sperm fibrous sheath. [provided by Alliance of Genome Resources, Apr 2022]

CASP8 (HGNC:1509): (caspase 8) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined. [provided by RefSeq, Jul 2008]

CASP8 Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome type 2B

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLACC1	NM_001127391.3	c.525-507G>T		intron_variant	Intron 7 of 14	ENST00000392257.8	NP_001120863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLACC1	ENST00000392257.8	c.525-507G>T		intron_variant	Intron 7 of 14	1	NM_001127391.3	ENSP00000376086.3

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96184 AN: 151714 Hom.: 31047 Cov.: 30

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.634 AC: 96267 AN: 151832 Hom.: 31085 Cov.: 30 AF XY: 0.637 AC XY: 47243 AN XY: 74218

African (AFR) AF: 0.737 AC: 30540 AN: 41428

American (AMR) AF: 0.493 AC: 7517 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1936 AN: 3462

East Asian (EAS) AF: 0.705 AC: 3627 AN: 5146

South Asian (SAS) AF: 0.790 AC: 3806 AN: 4818

European-Finnish (FIN) AF: 0.616 AC: 6474 AN: 10510

Middle Eastern (MID) AF: 0.610 AC: 177 AN: 290

European-Non Finnish (NFE) AF: 0.597 AC: 40533 AN: 67914

Other (OTH) AF: 0.579 AC: 1214 AN: 2098

Alfa AF: 0.607 Hom.: 88375

Bravo AF: 0.625

Asia WGS AF: 0.770 AC: 2678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.36
PhyloP100		0.015
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: rs9288318; hg19: chr2-202196063;