rs2951929

Variant names:

• chr6-75428844-A-G
• rs2951929
• NM_015687.5:c.-6-13866T>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.-6-13866T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 150,496 control chromosomes in the GnomAD database, including 37,363 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 (37363 hom., cov: 31)
• Consequence: FILIP1 NM_015687.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FILIP1	NM_015687.5	c.-6-13866T>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.-6-13866T>C		intron_variant	Intron 1 of 5	1	NM_015687.5	ENSP00000237172.7
FILIP1	ENST00000393004.6	c.-6-13866T>C		intron_variant	Intron 1 of 6	1		ENSP00000376728.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 104844 AN: 150402 Hom.: 37338 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.697 AC: 104900 AN: 150496 Hom.: 37363 Cov.: 31 AF XY: 0.692 AC XY: 50977 AN XY: 73620

African (AFR) AF: 0.854 AC: 34245 AN: 40080

American (AMR) AF: 0.565 AC: 8587 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3470

East Asian (EAS) AF: 0.584 AC: 3000 AN: 5140

South Asian (SAS) AF: 0.709 AC: 3424 AN: 4826

European-Finnish (FIN) AF: 0.597 AC: 6309 AN: 10562

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.663 AC: 45046 AN: 67926

Other (OTH) AF: 0.659 AC: 1382 AN: 2098

Alfa AF: 0.607 Hom.: 2136

Bravo AF: 0.700

Asia WGS AF: 0.627 AC: 2177 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.040
DANN	Benign	0.56
PhyloP100		-1.6
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: rs2951929; hg19: chr6-76138560;