1-93537256-T-G

Position:

• chr1-93537256-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164473.3(FNBP1L):​c.1149+766T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,870 control chromosomes in the GnomAD database, including 24,038 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 0.54 (24038 hom., cov: 31)
• Consequence: FNBP1L NM_001164473.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503

Genes affected

FNBP1L (HGNC:20851): (formin binding protein 1 like) The protein encoded by this gene binds to both CDC42 and N-WASP. This protein promotes CDC42-induced actin polymerization by activating the N-WASP-WIP complex and, therefore, is involved in a pathway that links cell surface signals to the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP1L	NM_001164473.3	c.1149+766T>G		intron_variant		ENST00000271234.13	NP_001157945.1
FNBP1L	NM_001024948.3	c.990+2348T>G		intron_variant			NP_001020119.1
FNBP1L	NM_017737.5	c.990+2348T>G		intron_variant			NP_060207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNBP1L	ENST00000271234.13	c.1149+766T>G		intron_variant		5	NM_001164473.3	ENSP00000271234.7
FNBP1L	ENST00000260506.12	c.990+2348T>G		intron_variant		1		ENSP00000260506.8
FNBP1L	ENST00000370253.6	c.990+2348T>G		intron_variant		5		ENSP00000359275.2
FNBP1L	ENST00000424449.2	c.684+766T>G		intron_variant		2		ENSP00000397451.2

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81516 AN: 151754 Hom.: 24028 Cov.: 31

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.537 AC: 81540 AN: 151870 Hom.: 24038 Cov.: 31 AF XY: 0.538 AC XY: 39954 AN XY: 74228

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.578

Alfa AF: 0.628 Hom.: 34059

Bravo AF: 0.513

Asia WGS AF: 0.572 AC: 1986 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.44

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: rs237438; hg19: chr1-94002813;