6-75476942-T-G

Position:

• chr6-75476942-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FILIP1	NM_015687.5	c.-7+16472A>C		intron_variant		ENST00000237172.12	NP_056502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FILIP1	ENST00000237172.12	c.-7+16472A>C		intron_variant		1	NM_015687.5	ENSP00000237172	P4
FILIP1	ENST00000393004.6	c.-7+16472A>C		intron_variant		1		ENSP00000376728	A1

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

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.197

Alfa AF: 0.153 Hom.: 4004

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9360910; hg19: chr6-76186658;