NM_015687.5:c.-6-32672G>T

Variant names:

• chr6-75447650-C-A
• rs2998394
• NM_015687.5:c.-6-32672G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015687.5(FILIP1):​c.-6-32672G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,990 control chromosomes in the GnomAD database, including 37,890 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 0.70 (37890 hom., cov: 32)
• Consequence: FILIP1 NM_015687.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 2 publications found

Genes affected

FILIP1 (HGNC:21015): (filamin A interacting protein 1) This gene encodes a filamin A binding protein. The encoded protein promotes the degradation of filamin A and may regulate cortical neuron migration and dendritic spine morphology. Mice lacking a functional copy of this gene exhibit reduced dendritic spine length and altered excitatory signaling. [provided by RefSeq, Oct 2016]

FILIP1 Gene-Disease associations (from GenCC):

• neuromuscular disorder, congenital, with dysmorphic facies

  Inheritance: AR Classification: MODERATE Submitted by: G2P

LOC101928540 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015687.5. 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
	FILIP1	NM_015687.5	MANE Select	c.-6-32672G>T		intron	N/A	NP_056502.1
	FILIP1	NM_001289987.3		c.3+6332G>T		intron	N/A	NP_001276916.1
	FILIP1	NM_001300866.3		c.-6-32672G>T		intron	N/A	NP_001287795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FILIP1	ENST00000237172.12	TSL:1 MANE Select	c.-6-32672G>T		intron	N/A	ENSP00000237172.7
	FILIP1	ENST00000393004.6	TSL:1	c.-6-32672G>T		intron	N/A	ENSP00000376728.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105936 AN: 151870 Hom.: 37853 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.698 AC: 106016 AN: 151990 Hom.: 37890 Cov.: 32 AF XY: 0.692 AC XY: 51448 AN XY: 74300

African (AFR) AF: 0.857 AC: 35566 AN: 41524

American (AMR) AF: 0.566 AC: 8636 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2180 AN: 3466

East Asian (EAS) AF: 0.585 AC: 3025 AN: 5168

South Asian (SAS) AF: 0.711 AC: 3432 AN: 4824

European-Finnish (FIN) AF: 0.585 AC: 6165 AN: 10544

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.662 AC: 44912 AN: 67894

Other (OTH) AF: 0.659 AC: 1390 AN: 2110

Alfa AF: 0.687 Hom.: 4757

Bravo AF: 0.699

Asia WGS AF: 0.629 AC: 2190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.096
DANN	Benign	0.49
PhyloP100		-2.0
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: rs2998394; hg19: chr6-76157366;