rs10197919

Positions:

• chr2-112167396-G-A
• chr2-112167396-G-C
• chr2-112167396-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153214.3(FBLN7):​c.406+2225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,884 control chromosomes in the GnomAD database, including 8,411 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 0.31 (8411 hom., cov: 32)
• Consequence: FBLN7 NM_153214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBLN7	NM_153214.3	c.406+2225G>A		intron_variant		ENST00000331203.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBLN7	ENST00000331203.7	c.406+2225G>A		intron_variant		1	NM_153214.3	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46862 AN: 151774 Hom.: 8411 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.309 AC: 46865 AN: 151884 Hom.: 8411 Cov.: 32 AF XY: 0.303 AC XY: 22512 AN XY: 74192

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.370

Alfa AF: 0.392 Hom.: 14022

Bravo AF: 0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs10197919; hg19: chr2-112924973;