rs2051616

Variant names:

• chr22-45567643-G-A
• rs2051616
• NM_006486.3:c.1698-6868G>A

Variant summary

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

The NM_006486.3(FBLN1):​c.1698-6868G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,818 control chromosomes in the GnomAD database, including 25,743 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 0.58 (25743 hom., cov: 31)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 3 publications found

Genes affected

FBLN1 (HGNC:3600): (fibulin 1) Fibulin 1 is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix. Calcium-binding is apparently required to mediate its binding to laminin and nidogen. It mediates platelet adhesion via binding fibrinogen. Four splice variants which differ in the 3' end have been identified. Each variant encodes a different isoform, but no functional distinctions have been identified among the four variants. [provided by RefSeq, Jul 2008]

FBLN1 Gene-Disease associations (from GenCC):

• FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• synpolydactyly type 2

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBLN1	NM_006486.3	c.1698-6868G>A		intron_variant	Intron 14 of 16	ENST00000327858.11	NP_006477.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBLN1	ENST00000327858.11	c.1698-6868G>A		intron_variant	Intron 14 of 16	1	NM_006486.3	ENSP00000331544.6

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88144 AN: 151700 Hom.: 25712 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.581 AC: 88216 AN: 151818 Hom.: 25743 Cov.: 31 AF XY: 0.580 AC XY: 43029 AN XY: 74162

African (AFR) AF: 0.632 AC: 26144 AN: 41398

American (AMR) AF: 0.570 AC: 8691 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2020 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2646 AN: 5148

South Asian (SAS) AF: 0.491 AC: 2362 AN: 4810

European-Finnish (FIN) AF: 0.585 AC: 6158 AN: 10528

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38289 AN: 67916

Other (OTH) AF: 0.580 AC: 1223 AN: 2108

Alfa AF: 0.569 Hom.: 23119

Bravo AF: 0.585

Asia WGS AF: 0.483 AC: 1682 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	0.95
DANN	Benign	0.48
PhyloP100		-0.16
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: rs2051616; hg19: chr22-45963523;