chr6-75432117-T-C

Variant names:

• chr6-75432117-T-C
• rs2951932
• NM_015687.5:c.-6-17139A>G

Variant summary

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

The NM_015687.5(FILIP1):​c.-6-17139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,064 control chromosomes in the GnomAD database, including 38,011 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 (38011 hom., cov: 32)
• Consequence: FILIP1 NM_015687.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• 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=-0.91).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FILIP1	NM_015687.5	MANE Select	c.-6-17139A>G		intron	N/A	NP_056502.1	Q7Z7B0-1
	FILIP1	NM_001289987.3		c.4-17139A>G		intron	N/A	NP_001276916.1
	FILIP1	NM_001300866.3		c.-6-17139A>G		intron	N/A	NP_001287795.1	Q7Z7B0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FILIP1	ENST00000237172.12	TSL:1 MANE Select	c.-6-17139A>G		intron	N/A	ENSP00000237172.7	Q7Z7B0-1
	FILIP1	ENST00000393004.6	TSL:1	c.-6-17139A>G		intron	N/A	ENSP00000376728.1	Q7Z7B0-2
	FILIP1	ENST00000865871.1		c.-6-17139A>G		intron	N/A	ENSP00000535930.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106250 AN: 151948 Hom.: 37974 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.699 AC: 106329 AN: 152064 Hom.: 38011 Cov.: 32 AF XY: 0.695 AC XY: 51623 AN XY: 74326

African (AFR) AF: 0.857 AC: 35562 AN: 41512

American (AMR) AF: 0.567 AC: 8664 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2181 AN: 3470

East Asian (EAS) AF: 0.584 AC: 3014 AN: 5158

South Asian (SAS) AF: 0.710 AC: 3423 AN: 4822

European-Finnish (FIN) AF: 0.596 AC: 6294 AN: 10554

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45073 AN: 67968

Other (OTH) AF: 0.661 AC: 1393 AN: 2108

Alfa AF: 0.689 Hom.: 4765

Bravo AF: 0.700

Asia WGS AF: 0.628 AC: 2180 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.62
PhyloP100		-2.4
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: rs2951932; hg19: chr6-76141833; COSMIC: COSV107250149; COSMIC: COSV107250149;