chr1-93546730-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164473.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP1L	NM_001164473.3	MANE Select	c.1275-112G>A		intron	N/A	NP_001157945.1
	FNBP1L	NM_001024948.3		c.1101-112G>A		intron	N/A	NP_001020119.1
	FNBP1L	NM_017737.5		c.1101-112G>A		intron	N/A	NP_060207.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNBP1L	ENST00000271234.13	TSL:5 MANE Select	c.1275-112G>A		intron	N/A	ENSP00000271234.7
	FNBP1L	ENST00000260506.12	TSL:1	c.1101-112G>A		intron	N/A	ENSP00000260506.8
	FNBP1L	ENST00000868905.1		c.1260-112G>A		intron	N/A	ENSP00000538964.1

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

African (AFR) AF: 0.826 AC: 17148 AN: 20758

American (AMR) AF: 0.887 AC: 19725 AN: 22246

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 15096 AN: 19192

East Asian (EAS) AF: 1.00 AC: 33850 AN: 33856

South Asian (SAS) AF: 0.971 AC: 58305 AN: 60048

European-Finnish (FIN) AF: 0.843 AC: 39061 AN: 46310

Middle Eastern (MID) AF: 0.840 AC: 3035 AN: 3612

European-Non Finnish (NFE) AF: 0.808 AC: 563979 AN: 698088

Other (OTH) AF: 0.829 AC: 35098 AN: 42360

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

African (AFR) AF: 0.824 AC: 34166 AN: 41474

American (AMR) AF: 0.852 AC: 13013 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2744 AN: 3466

East Asian (EAS) AF: 0.999 AC: 5187 AN: 5192

South Asian (SAS) AF: 0.972 AC: 4697 AN: 4830

European-Finnish (FIN) AF: 0.855 AC: 9048 AN: 10580

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55031 AN: 67956

Other (OTH) AF: 0.840 AC: 1775 AN: 2112

Alfa AF: 0.815 Hom.: 99018

Bravo AF: 0.829

Asia WGS AF: 0.970 AC: 3375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.69
PhyloP100		-0.23
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: rs237425; hg19: chr1-94012287;