chr6-75457782-G-T

Variant names:

• chr6-75457782-G-T
• rs2808182
• NM_015687.5:c.-7+35632C>A

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+35632C>A 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 152,070 control chromosomes in the GnomAD database, including 38,073 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 (38073 hom., cov: 32)
• Consequence: FILIP1 NM_015687.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570
• 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

ENSG00000238156 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 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.-7+35632C>A		intron	N/A	NP_056502.1	Q7Z7B0-1
	FILIP1	NM_001289987.3		c.-163-3635C>A		intron	N/A	NP_001276916.1
	FILIP1	NM_001300866.3		c.-7+35632C>A		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.-7+35632C>A		intron	N/A	ENSP00000237172.7	Q7Z7B0-1
	FILIP1	ENST00000393004.6	TSL:1	c.-7+35632C>A		intron	N/A	ENSP00000376728.1	Q7Z7B0-2
	FILIP1	ENST00000865871.1		c.-7+35632C>A		intron	N/A	ENSP00000535930.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106207 AN: 151952 Hom.: 38044 Cov.: 32

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.699 AC: 106278 AN: 152070 Hom.: 38073 Cov.: 32 AF XY: 0.694 AC XY: 51590 AN XY: 74314

African (AFR) AF: 0.863 AC: 35829 AN: 41526

American (AMR) AF: 0.568 AC: 8677 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2221 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2761 AN: 5172

South Asian (SAS) AF: 0.724 AC: 3491 AN: 4820

European-Finnish (FIN) AF: 0.594 AC: 6252 AN: 10530

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44902 AN: 67966

Other (OTH) AF: 0.664 AC: 1402 AN: 2112

Alfa AF: 0.610 Hom.: 3150

Bravo AF: 0.700

Asia WGS AF: 0.613 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.36
DANN	Benign	0.59
PhyloP100		-0.57
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: rs2808182; hg19: chr6-76167498; COSMIC: COSV107250153;