6-75461797-T-C

Variant names:

• chr6-75461797-T-C
• rs2998367
• NM_015687.5:c.-7+31617A>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.-7+31617A>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 152,160 control chromosomes in the GnomAD database, including 38,121 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 (38121 hom., cov: 33)
• Consequence: FILIP1 NM_015687.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• Publications: 7 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 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.-7+31617A>G		intron	N/A	NP_056502.1
	FILIP1	NM_001289987.3		c.-163-7650A>G		intron	N/A	NP_001276916.1
	FILIP1	NM_001300866.3		c.-7+31617A>G		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.-7+31617A>G		intron	N/A	ENSP00000237172.7
	FILIP1	ENST00000393004.6	TSL:1	c.-7+31617A>G		intron	N/A	ENSP00000376728.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106281 AN: 152044 Hom.: 38092 Cov.: 33

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.699 AC: 106352 AN: 152160 Hom.: 38121 Cov.: 33 AF XY: 0.694 AC XY: 51625 AN XY: 74380

African (AFR) AF: 0.863 AC: 35845 AN: 41534

American (AMR) AF: 0.568 AC: 8682 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2221 AN: 3470

East Asian (EAS) AF: 0.540 AC: 2783 AN: 5158

South Asian (SAS) AF: 0.725 AC: 3497 AN: 4822

European-Finnish (FIN) AF: 0.593 AC: 6273 AN: 10582

Middle Eastern (MID) AF: 0.709 AC: 207 AN: 292

European-Non Finnish (NFE) AF: 0.660 AC: 44912 AN: 68006

Other (OTH) AF: 0.663 AC: 1396 AN: 2104

Alfa AF: 0.662 Hom.: 93689

Bravo AF: 0.700

Asia WGS AF: 0.622 AC: 2167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.3
DANN	Benign	0.67
PhyloP100		-0.78
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: rs2998367; hg19: chr6-76171513;