rs17383714

Variant names:

• chr2-201289066-C-T
• rs17383714
• NM_001127391.3:c.1143-285G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127391.3(FLACC1):​c.1143-285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 152,278 control chromosomes in the GnomAD database, including 422 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 0.063 (422 hom., cov: 33)
• Consequence: FLACC1 NM_001127391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLACC1	NM_001127391.3	c.1143-285G>A		intron_variant	Intron 14 of 14	ENST00000392257.8	NP_001120863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLACC1	ENST00000392257.8	c.1143-285G>A		intron_variant	Intron 14 of 14	1	NM_001127391.3	ENSP00000376086.3

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9659 AN: 152160 Hom.: 424 Cov.: 33

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0944

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0828

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

GnomAD4 genome AF: 0.0634 AC: 9654 AN: 152278 Hom.: 422 Cov.: 33 AF XY: 0.0640 AC XY: 4762 AN XY: 74442

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0596

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0941

Gnomad4 FIN AF: 0.0868

Gnomad4 NFE AF: 0.0891

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.0830 Hom.: 147

Bravo AF: 0.0567

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs17383714; hg19: chr2-202153789;