rs78261087

Positions:

• chr11-47743354-G-A
• chr11-47743354-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015308.5(FNBP4):​c.1456+599C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,122 control chromosomes in the GnomAD database, including 37 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 0.020 (37 hom., cov: 32)
• Consequence: FNBP4 NM_015308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

Genes affected

FNBP4 (HGNC:19752): (formin binding protein 4) This gene encodes a protein containing two tryptophan-rich WW domains that binds the proline-rich formin homology 1 domains of formin family proteins, suggesting a role in the regulation of cytoskeletal dynamics during cell division and migration. It also binds intersectin family proteins suggesting a role in the maintenance of membrane curvature at sites of nascent vesicle formation. Naturally occurring mutations in this gene are associated with Waardenburg anophthalmia syndrome. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0196 (2986/152122) while in subpopulation AFR AF= 0.0294 (1221/41508). AF 95% confidence interval is 0.028. There are 37 homozygotes in gnomad4. There are 1386 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNBP4	NM_015308.5	c.1456+599C>T		intron_variant		ENST00000263773.10	NP_056123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNBP4	ENST00000263773.10	c.1456+599C>T		intron_variant		1	NM_015308.5	ENSP00000263773	P1
FNBP4	ENST00000527894.1	n.191+599C>T		intron_variant, non_coding_transcript_variant		3
FNBP4	ENST00000528388.5	n.63+599C>T		intron_variant, non_coding_transcript_variant		2
FNBP4	ENST00000534003.5	n.1454+599C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2984 AN: 152004 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00457

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0196 AC: 2986 AN: 152122 Hom.: 37 Cov.: 32 AF XY: 0.0186 AC XY: 1386 AN XY: 74384

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00457

Gnomad4 FIN AF: 0.00613

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.00514 Hom.: 1

Bravo AF: 0.0216

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.48

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: rs78261087; hg19: chr11-47764906;