rs6914322

Positions:

• chr6-109785538-A-T

Variant summary

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

The NM_014845.6(FIG4):​c.1948+510A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 305,294 control chromosomes in the GnomAD database, including 19,732 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 (12683 hom., cov: 33)
  • Exomes 𝑓: 0.26 (7049 hom.)
• Consequence: FIG4 NM_014845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

Genes affected

FIG4 (HGNC:16873): (FIG4 phosphoinositide 5-phosphatase) The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIG4	NM_014845.6	c.1948+510A>T		intron_variant		ENST00000230124.8
FIG4	XM_011536281.4	c.1885+510A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIG4	ENST00000230124.8	c.1948+510A>T		intron_variant		1	NM_014845.6	P4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51281 AN: 151996 Hom.: 12642 Cov.: 33

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.259 AC: 39656 AN: 153180 Hom.: 7049 AF XY: 0.273 AC XY: 23248 AN XY: 85032

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.338 AC: 51391 AN: 152114 Hom.: 12683 Cov.: 33 AF XY: 0.342 AC XY: 25440 AN XY: 74364

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.303

Alfa AF: 0.262 Hom.: 985

Bravo AF: 0.350

Asia WGS AF: 0.445 AC: 1542 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.3
DANN	Benign	0.68

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: rs6914322; hg19: chr6-110106741; COSMIC: COSV57786157; COSMIC: COSV57786157;