rs984261801

Variant names:

• chr22-45503015-C-A
• rs984261801
• NM_006486.3:c.30C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-45503015-C-A
• chr22-45503015-C-G
• chr22-45503015-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_006486.3(FBLN1):​c.30C>A​(p.Val10Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,094,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: FBLN1 NM_006486.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.332
• 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 22-45503015-C-A is Benign according to our data. Variant chr22-45503015-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 756467.Status of the report is criteria_provided_single_submitter, 1 stars.

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.30C>A	p.Val10Val	synonymous	Exon 1 of 17	NP_006477.3
	FBLN1	NM_001996.4		c.30C>A	p.Val10Val	synonymous	Exon 1 of 15	NP_001987.3
	FBLN1	NM_006485.4		c.30C>A	p.Val10Val	synonymous	Exon 1 of 15	NP_006476.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBLN1	ENST00000327858.11	TSL:1 MANE Select	c.30C>A	p.Val10Val	synonymous	Exon 1 of 17	ENSP00000331544.6	P23142-1
	FBLN1	ENST00000262722.11	TSL:1	c.30C>A	p.Val10Val	synonymous	Exon 1 of 15	ENSP00000262722.7	P23142-4
	FBLN1	ENST00000442170.6	TSL:1	c.30C>A	p.Val10Val	synonymous	Exon 1 of 15	ENSP00000393812.2	P23142-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000700 AC: 1 AN: 14290 AF XY: 0.000113

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000487

Gnomad ASJ exome AF: 0.00

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: 0.0000119 AC: 13 AN: 1094084 Hom.: 0 Cov.: 30 AF XY: 0.0000133 AC XY: 7 AN XY: 524496

African (AFR) AF: 0.00 AC: 0 AN: 22526

American (AMR) AF: 0.000100 AC: 1 AN: 9994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14458

East Asian (EAS) AF: 0.00 AC: 0 AN: 25204

South Asian (SAS) AF: 0.00 AC: 0 AN: 25308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2972

European-Non Finnish (NFE) AF: 0.0000129 AC: 12 AN: 928574

Other (OTH) AF: 0.00 AC: 0 AN: 43384

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

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	-0.38
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		-0.33
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs984261801; hg19: chr22-45898895;