rs4849056

Variant names:

• chr2-112208932-G-A
• rs4849056
• XR_007069507.1:n.1219-12664G>A

Variant summary

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

The XR_007069507.1(FBLN7):​n.1219-12664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,044 control chromosomes in the GnomAD database, including 5,984 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 0.25 (5984 hom., cov: 31)
• Consequence: FBLN7 XR_007069507.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 9 publications found

Genes affected

FBLN7 (HGNC:26740): (fibulin 7) Predicted to enable calcium ion binding activity; heparan sulfate proteoglycan binding activity; and heparin binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within positive regulation of biomineralization. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBLN7	XR_007069507.1	n.1219-12664G>A		intron_variant	Intron 7 of 9
FBLN7	XR_007069508.1	n.1219-12664G>A		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38453 AN: 151926 Hom.: 5984 Cov.: 31

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.253 AC: 38447 AN: 152044 Hom.: 5984 Cov.: 31 AF XY: 0.250 AC XY: 18581 AN XY: 74306

African (AFR) AF: 0.0697 AC: 2891 AN: 41502

American (AMR) AF: 0.236 AC: 3597 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1252 AN: 5164

South Asian (SAS) AF: 0.254 AC: 1223 AN: 4810

European-Finnish (FIN) AF: 0.322 AC: 3394 AN: 10556

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23833 AN: 67954

Other (OTH) AF: 0.300 AC: 633 AN: 2112

Alfa AF: 0.321 Hom.: 26935

Bravo AF: 0.238

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.5
DANN	Benign	0.76
PhyloP100		0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4849056; hg19: chr2-112966509;