6-75476942-T-G

Variant names:

• chr6-75476942-T-G
• rs9360910
• NM_015687.5:c.-7+16472A>C

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+16472A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,082 control chromosomes in the GnomAD database, including 3,854 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 0.21 (3854 hom., cov: 32)
• Consequence: FILIP1 NM_015687.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FILIP1	NM_015687.5	c.-7+16472A>C		intron_variant	Intron 1 of 5	ENST00000237172.12	NP_056502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FILIP1	ENST00000237172.12	c.-7+16472A>C		intron_variant	Intron 1 of 5	1	NM_015687.5	ENSP00000237172.7
FILIP1	ENST00000393004.6	c.-7+16472A>C		intron_variant	Intron 1 of 6	1		ENSP00000376728.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31874 AN: 151964 Hom.: 3857 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.210 AC: 31883 AN: 152082 Hom.: 3854 Cov.: 32 AF XY: 0.210 AC XY: 15595 AN XY: 74346

African (AFR) AF: 0.331 AC: 13741 AN: 41474

American (AMR) AF: 0.186 AC: 2834 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1304 AN: 5178

South Asian (SAS) AF: 0.225 AC: 1081 AN: 4810

European-Finnish (FIN) AF: 0.163 AC: 1723 AN: 10572

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9741 AN: 68000

Other (OTH) AF: 0.197 AC: 414 AN: 2106

Alfa AF: 0.166 Hom.: 7623

Bravo AF: 0.218

Asia WGS AF: 0.240 AC: 832 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.79
DANN	Benign	0.57
PhyloP100		-0.18
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: rs9360910; hg19: chr6-76186658;