rs6715284

Variant names:

• chr2-201289674-C-G
• rs6715284
• NM_001127391.3:c.1032+22G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-201289674-C-G
• chr2-201289674-C-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.1032+22G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,611,832 control chromosomes in the GnomAD database, including 14,226 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 0.18 (3836 hom., cov: 31)
  • Exomes 𝑓: 0.10 (10390 hom.)
• Consequence: FLACC1 NM_001127391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 38 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLACC1	NM_001127391.3	MANE Select	c.1032+22G>C		intron	N/A	NP_001120863.1	Q96Q35-2
	FLACC1	NM_139163.4		c.1101+22G>C		intron	N/A	NP_631902.2	Q96Q35-1
	FLACC1	NM_001289993.2		c.1032+22G>C		intron	N/A	NP_001276922.1	Q96Q35-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLACC1	ENST00000392257.8	TSL:1 MANE Select	c.1032+22G>C		intron	N/A	ENSP00000376086.3	Q96Q35-2
	FLACC1	ENST00000286190.9	TSL:1	c.1101+22G>C		intron	N/A	ENSP00000286190.5	Q96Q35-1
	FLACC1	ENST00000405148.6	TSL:5	c.1101+22G>C		intron	N/A	ENSP00000385098.2	Q96Q35-1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27310 AN: 151986 Hom.: 3833 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.117 AC: 29344 AN: 249832 AF XY: 0.119

Gnomad AFR exome AF: 0.396

Gnomad AMR exome AF: 0.0710

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0128

Gnomad FIN exome AF: 0.0575

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.104 AC: 152487 AN: 1459728 Hom.: 10390 Cov.: 33 AF XY: 0.107 AC XY: 77662 AN XY: 725976

African (AFR) AF: 0.394 AC: 13182 AN: 33444

American (AMR) AF: 0.0762 AC: 3403 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2673 AN: 25992

East Asian (EAS) AF: 0.00666 AC: 264 AN: 39668

South Asian (SAS) AF: 0.193 AC: 16595 AN: 86076

European-Finnish (FIN) AF: 0.0581 AC: 3096 AN: 53282

Middle Eastern (MID) AF: 0.102 AC: 585 AN: 5750

European-Non Finnish (NFE) AF: 0.0952 AC: 105764 AN: 1110596

Other (OTH) AF: 0.115 AC: 6925 AN: 60290

GnomAD4 genome AF: 0.180 AC: 27334 AN: 152104 Hom.: 3836 Cov.: 31 AF XY: 0.176 AC XY: 13057 AN XY: 74378

African (AFR) AF: 0.388 AC: 16083 AN: 41414

American (AMR) AF: 0.116 AC: 1771 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3470

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5192

South Asian (SAS) AF: 0.195 AC: 937 AN: 4816

European-Finnish (FIN) AF: 0.0536 AC: 569 AN: 10612

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7124 AN: 68008

Other (OTH) AF: 0.150 AC: 316 AN: 2112

Alfa AF: 0.0768 Hom.: 109

Bravo AF: 0.190

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		-0.38
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: rs6715284; hg19: chr2-202154397;