rs7292978

Variant names:

• chr22-45518581-G-A
• rs7292978
• NM_006486.3:c.80-101G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-45518581-G-A
• chr22-45518581-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006486.3(FBLN1):​c.80-101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 868,698 control chromosomes in the GnomAD database, including 29,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4494 hom., cov: 31)
  • Exomes 𝑓: 0.25 (24964 hom.)
• Consequence: FBLN1 NM_006486.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.781
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-45518581-G-A is Benign according to our data. Variant chr22-45518581-G-A is described in ClinVar as Benign. ClinVar VariationId is 1181351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

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.80-101G>A		intron	N/A	NP_006477.3
	FBLN1	NM_001996.4		c.80-101G>A		intron	N/A	NP_001987.3
	FBLN1	NM_006485.4		c.80-101G>A		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.80-101G>A		intron	N/A	ENSP00000331544.6	P23142-1
	FBLN1	ENST00000262722.11	TSL:1	c.80-101G>A		intron	N/A	ENSP00000262722.7	P23142-4
	FBLN1	ENST00000442170.6	TSL:1	c.80-101G>A		intron	N/A	ENSP00000393812.2	P23142-3

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35661 AN: 151824 Hom.: 4492 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0533

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.254 AC: 181781 AN: 716756 Hom.: 24964 Cov.: 9 AF XY: 0.250 AC XY: 94518 AN XY: 377682

African (AFR) AF: 0.174 AC: 3271 AN: 18812

American (AMR) AF: 0.166 AC: 5774 AN: 34838

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 4770 AN: 20994

East Asian (EAS) AF: 0.0405 AC: 1321 AN: 32640

South Asian (SAS) AF: 0.156 AC: 10200 AN: 65594

European-Finnish (FIN) AF: 0.272 AC: 11381 AN: 41770

Middle Eastern (MID) AF: 0.198 AC: 768 AN: 3886

European-Non Finnish (NFE) AF: 0.293 AC: 135477 AN: 462496

Other (OTH) AF: 0.247 AC: 8819 AN: 35726

GnomAD4 genome AF: 0.235 AC: 35655 AN: 151942 Hom.: 4494 Cov.: 31 AF XY: 0.233 AC XY: 17327 AN XY: 74280

African (AFR) AF: 0.172 AC: 7115 AN: 41436

American (AMR) AF: 0.221 AC: 3381 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 814 AN: 3472

East Asian (EAS) AF: 0.0532 AC: 275 AN: 5170

South Asian (SAS) AF: 0.147 AC: 705 AN: 4808

European-Finnish (FIN) AF: 0.272 AC: 2870 AN: 10556

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19614 AN: 67914

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.268 Hom.: 9850

Bravo AF: 0.228

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.41
PhyloP100		0.78
PromoterAI		0.0036	Neutral
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: rs7292978; hg19: chr22-45914461; COSMIC: COSV53048631; COSMIC: COSV53048631;