NM_001319193.2:c.-84+276C>G

Variant names:

• chr17-75940572-G-C
• rs2608881
• NM_001319193.2:c.-84+276C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001319193.2(FBF1):​c.-84+276C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 153,118 control chromosomes in the GnomAD database, including 4,604 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 0.24 (4572 hom., cov: 32)
  • Exomes 𝑓: 0.22 (32 hom.)
• Consequence: FBF1 NM_001319193.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 19 publications found

Genes affected

FBF1 (HGNC:24674): (Fas binding factor 1) Involved in apical junction assembly and establishment of epithelial cell polarity. Acts upstream of or within cilium assembly. Located in centriole; centrosome; and spindle pole. Part of ciliary transition fiber. Colocalizes with apical junction complex and keratin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBF1	NM_001319193.2	c.-84+276C>G		intron_variant	Intron 1 of 29	ENST00000636174.2	NP_001306122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBF1	ENST00000636174.2	c.-84+276C>G		intron_variant	Intron 1 of 29	5	NM_001319193.2	ENSP00000490726.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36692 AN: 151880 Hom.: 4565 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.224 AC: 251 AN: 1120 Hom.: 32 Cov.: 0 AF XY: 0.234 AC XY: 144 AN XY: 616

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.125 AC: 1 AN: 8

European-Finnish (FIN) AF: 0.218 AC: 196 AN: 900

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.255 AC: 47 AN: 184

Other (OTH) AF: 0.350 AC: 7 AN: 20

GnomAD4 genome AF: 0.242 AC: 36715 AN: 151998 Hom.: 4572 Cov.: 32 AF XY: 0.235 AC XY: 17469 AN XY: 74300

African (AFR) AF: 0.229 AC: 9476 AN: 41448

American (AMR) AF: 0.210 AC: 3204 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 994 AN: 3466

East Asian (EAS) AF: 0.157 AC: 807 AN: 5154

South Asian (SAS) AF: 0.192 AC: 927 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2062 AN: 10570

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18336 AN: 67964

Other (OTH) AF: 0.262 AC: 551 AN: 2106

Alfa AF: 0.147 Hom.: 292

Bravo AF: 0.246

Asia WGS AF: 0.216 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.4
DANN	Benign	0.75
PhyloP100		1.4
PromoterAI		-0.078	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2608881; hg19: chr17-73936653;