rs237425

Variant names:

• chr1-93546730-G-A
• rs237425
• NM_001164473.3:c.1275-112G>A

Variant summary

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

The NM_001164473.3(FNBP1L):​c.1275-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 1,098,556 control chromosomes in the GnomAD database, including 380,533 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 0.83 (52902 hom., cov: 31)
  • Exomes 𝑓: 0.83 (327631 hom.)
• Consequence: FNBP1L NM_001164473.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP1L	NM_001164473.3	c.1275-112G>A		intron_variant	Intron 12 of 16	ENST00000271234.13	NP_001157945.1
FNBP1L	NM_001024948.3	c.1101-112G>A		intron_variant	Intron 10 of 13		NP_001020119.1
FNBP1L	NM_017737.5	c.1101-112G>A		intron_variant	Intron 10 of 14		NP_060207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNBP1L	ENST00000271234.13	c.1275-112G>A		intron_variant	Intron 12 of 16	5	NM_001164473.3	ENSP00000271234.7

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126463 AN: 151968 Hom.: 52847 Cov.: 31

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.830 AC: 785297 AN: 946470 Hom.: 327631 AF XY: 0.834 AC XY: 401550 AN XY: 481286

Gnomad4 AFR exome AF: 0.826

Gnomad4 AMR exome AF: 0.887

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.971

Gnomad4 FIN exome AF: 0.843

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.829

GnomAD4 genome AF: 0.832 AC: 126578 AN: 152086 Hom.: 52902 Cov.: 31 AF XY: 0.836 AC XY: 62142 AN XY: 74342

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.840

Alfa AF: 0.815 Hom.: 71973

Bravo AF: 0.829

Asia WGS AF: 0.970 AC: 3375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.69

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: rs237425; hg19: chr1-94012287;