NM_006486.3:c.79+14G>C

Variant names:

• chr22-45503078-G-C
• rs545228163
• NM_006486.3:c.79+14G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006486.3(FBLN1):​c.79+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000479 in 1,231,462 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00044 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (2 hom.)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.388
• Publications: 0 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: AR, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 22-45503078-G-C is Benign according to our data. Variant chr22-45503078-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3021231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006486.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN1	NM_006486.3	MANE Select	c.79+14G>C		intron	N/A	NP_006477.3
	FBLN1	NM_001996.4		c.79+14G>C		intron	N/A	NP_001987.3
	FBLN1	NM_006485.4		c.79+14G>C		intron	N/A	NP_006476.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN1	ENST00000327858.11	TSL:1 MANE Select	c.79+14G>C		intron	N/A	ENSP00000331544.6	P23142-1
	FBLN1	ENST00000262722.11	TSL:1	c.79+14G>C		intron	N/A	ENSP00000262722.7	P23142-4
	FBLN1	ENST00000442170.6	TSL:1	c.79+14G>C		intron	N/A	ENSP00000393812.2	P23142-3

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 67 AN: 151916 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.00924

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000554 AC: 2 AN: 3610 AF XY: 0.000428

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00314

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000485 AC: 523 AN: 1079436 Hom.: 2 Cov.: 30 AF XY: 0.000505 AC XY: 259 AN XY: 512910

African (AFR) AF: 0.000223 AC: 5 AN: 22404

American (AMR) AF: 0.000593 AC: 5 AN: 8436

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 160 AN: 13958

East Asian (EAS) AF: 0.00 AC: 0 AN: 25626

South Asian (SAS) AF: 0.0000877 AC: 2 AN: 22808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21206

Middle Eastern (MID) AF: 0.00752 AC: 24 AN: 3190

European-Non Finnish (NFE) AF: 0.000309 AC: 284 AN: 918830

Other (OTH) AF: 0.00100 AC: 43 AN: 42978

GnomAD4 genome AF: 0.000441 AC: 67 AN: 152026 Hom.: 1 Cov.: 32 AF XY: 0.000431 AC XY: 32 AN XY: 74316

African (AFR) AF: 0.0000482 AC: 2 AN: 41524

American (AMR) AF: 0.000655 AC: 10 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00924 AC: 32 AN: 3462

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000280 AC: 19 AN: 67906

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000601

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.6
DANN	Benign	0.83
PhyloP100		-0.39
PromoterAI		0.060	Neutral
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: rs545228163; hg19: chr22-45898958;