rs1406121

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000392257.8(FLACC1):​c.675+163A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,908 control chromosomes in the GnomAD database, including 13,308 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 0.40 ( 13308 hom., cov: 31)

Consequence

FLACC1
ENST00000392257.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.839
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FLACC1NM_001127391.3 linkuse as main transcriptc.675+163A>G intron_variant ENST00000392257.8 NP_001120863.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FLACC1ENST00000392257.8 linkuse as main transcriptc.675+163A>G intron_variant 1 NM_001127391.3 ENSP00000376086 P1Q96Q35-2

Frequencies

GnomAD3 genomes
AF:
0.403
AC:
61104
AN:
151790
Hom.:
13315
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.226
Gnomad AMI
AF:
0.421
Gnomad AMR
AF:
0.350
Gnomad ASJ
AF:
0.414
Gnomad EAS
AF:
0.448
Gnomad SAS
AF:
0.545
Gnomad FIN
AF:
0.524
Gnomad MID
AF:
0.405
Gnomad NFE
AF:
0.490
Gnomad OTH
AF:
0.375
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.402
AC:
61087
AN:
151908
Hom.:
13308
Cov.:
31
AF XY:
0.404
AC XY:
30015
AN XY:
74226
show subpopulations
Gnomad4 AFR
AF:
0.225
Gnomad4 AMR
AF:
0.349
Gnomad4 ASJ
AF:
0.414
Gnomad4 EAS
AF:
0.447
Gnomad4 SAS
AF:
0.545
Gnomad4 FIN
AF:
0.524
Gnomad4 NFE
AF:
0.490
Gnomad4 OTH
AF:
0.372
Alfa
AF:
0.464
Hom.:
5883
Bravo
AF:
0.381
Asia WGS
AF:
0.482
AC:
1674
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.2
DANN
Benign
0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1406121; hg19: chr2-202195030; API