rs78261087

Variant names:

• chr11-47743354-G-A
• rs78261087
• NM_015308.5:c.1456+599C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNBP4	NM_015308.5	c.1456+599C>T		intron_variant	Intron 8 of 16	ENST00000263773.10	NP_056123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNBP4	ENST00000263773.10	c.1456+599C>T		intron_variant	Intron 8 of 16	1	NM_015308.5	ENSP00000263773.5
FNBP4	ENST00000527894.1	n.191+599C>T		intron_variant	Intron 1 of 3	3
FNBP4	ENST00000528388.5	n.63+599C>T		intron_variant	Intron 1 of 4	2
FNBP4	ENST00000534003.5	n.1454+599C>T		intron_variant	Intron 8 of 10	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

African (AFR) AF: 0.0294 AC: 1221 AN: 41508

American (AMR) AF: 0.0217 AC: 331 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00457 AC: 22 AN: 4814

European-Finnish (FIN) AF: 0.00613 AC: 65 AN: 10604

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0172 AC: 1172 AN: 67992

Other (OTH) AF: 0.0222 AC: 47 AN: 2114

Alfa AF: 0.00559 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
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism

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: rs78261087; hg19: chr11-47764906;