rs10199110

Variant names:

• chr2-201304060-G-C
• rs10199110
• NM_001127391.3:c.879+3459C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-201304060-G-C
• chr2-201304060-G-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.879+3459C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,098 control chromosomes in the GnomAD database, including 3,375 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 0.20 (3375 hom., cov: 31)
• Consequence: FLACC1 NM_001127391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLACC1	NM_001127391.3	MANE Select	c.879+3459C>G		intron	N/A	NP_001120863.1
	FLACC1	NM_139163.4		c.879+3459C>G		intron	N/A	NP_631902.2
	FLACC1	NM_001289993.2		c.879+3459C>G		intron	N/A	NP_001276922.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLACC1	ENST00000392257.8	TSL:1 MANE Select	c.879+3459C>G		intron	N/A	ENSP00000376086.3
	FLACC1	ENST00000286190.9	TSL:1	c.879+3459C>G		intron	N/A	ENSP00000286190.5
	FLACC1	ENST00000405148.6	TSL:5	c.879+3459C>G		intron	N/A	ENSP00000385098.2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30701 AN: 151980 Hom.: 3356 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.202 AC: 30773 AN: 152098 Hom.: 3375 Cov.: 31 AF XY: 0.202 AC XY: 15016 AN XY: 74356

African (AFR) AF: 0.277 AC: 11484 AN: 41486

American (AMR) AF: 0.136 AC: 2079 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 505 AN: 3472

East Asian (EAS) AF: 0.203 AC: 1052 AN: 5170

South Asian (SAS) AF: 0.301 AC: 1448 AN: 4818

European-Finnish (FIN) AF: 0.137 AC: 1446 AN: 10554

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.176 AC: 11942 AN: 67990

Other (OTH) AF: 0.208 AC: 441 AN: 2116

Alfa AF: 0.0754 Hom.: 95

Bravo AF: 0.203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.69
PhyloP100		0.22
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: rs10199110; hg19: chr2-202168783;