rs11674814

chr2-201289123-G-Achr2-201289123-G-C

Variant summary

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

The NM_001127391.3(FLACC1):c.1142+334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,108 control chromosomes in the GnomAD database, including 10,177 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 0.34 (10177 hom., cov: 33)
• Consequence: FLACC1 NM_001127391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLACC1	NM_001127391.3	c.1142+334C>T		intron_variant		ENST00000392257.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLACC1	ENST00000392257.8	c.1142+334C>T		intron_variant		1	NM_001127391.3	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51405 AN: 151990 Hom.: 10181 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.338 AC: 51389 AN: 152108 Hom.: 10177 Cov.: 33 AF XY: 0.339 AC XY: 25190 AN XY: 74340

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.322

Alfa AF: 0.375 Hom.: 1852

Bravo AF: 0.321

Asia WGS AF: 0.380 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.9
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs11674814; hg19: chr2-202153846;