2-201289477-C-T

Position:

chr2-201289477-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001127391.3(FLACC1):c.1122G>A(p.Thr374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,772 control chromosomes in the GnomAD database, including 11,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 810 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11158 hom. )

Consequence

FLACC1
NM_001127391.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.573

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]

FLACC1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-201289477-C-T is Benign according to our data. Variant chr2-201289477-C-T is described in ClinVar as [Benign]. Clinvar id is 402494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.573 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLACC1	NM_001127391.3 linkuse as main transcript	c.1122G>A	p.Thr374=	synonymous_variant	14/15	ENST00000392257.8	NP_001120863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLACC1	ENST00000392257.8 linkuse as main transcript	c.1122G>A	p.Thr374=	synonymous_variant	14/15	1	NM_001127391.3	ENSP00000376086	P1	Q96Q35-2

Frequencies

GnomAD3 genomes

AF:

0.0967

AC:

14711

AN:

152154

Hom.:

808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0622

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.0864

Gnomad ASJ

AF:

0.0637

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0381

Gnomad FIN

AF:

0.0979

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.0896

AC:

22515

AN:

251398

Hom.:

1291

AF XY:

0.0891

AC XY:

12111

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0615

Gnomad AMR exome

AF:

0.0571

Gnomad ASJ exome

AF:

0.0606

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0437

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.117

AC:

171047

AN:

1461500

Hom.:

11158

Cov.:

AF XY:

0.115

AC XY:

83650

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.0577

Gnomad4 AMR exome

AF:

0.0601

Gnomad4 ASJ exome

AF:

0.0646

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0467

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0968

AC:

14733

AN:

152272

Hom.:

810

Cov.:

AF XY:

0.0932

AC XY:

6942

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0627

Gnomad4 AMR

AF:

0.0862

Gnomad4 ASJ

AF:

0.0637

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0385

Gnomad4 FIN

AF:

0.0979

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.119

Hom.:

1917

Bravo

AF:

0.0947

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.1

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over