6-75428844-A-G

Position:

• chr6-75428844-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC101928540 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
FILIP1	NM_015687.5	c.-6-13866T>C		intron_variant		ENST00000237172.12
LOC101928540	NR_125859.1	n.208+13648A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FILIP1	ENST00000237172.12	c.-6-13866T>C		intron_variant		1	NM_015687.5	P4
FILIP1	ENST00000393004.6	c.-6-13866T>C		intron_variant		1		A1

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

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.659

Alfa AF: 0.587 Hom.: 1854

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

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: rs2951929; hg19: chr6-76138560;