rs1848501

Positions:

• chr5-128436294-G-A

Variant summary

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

The NM_001999.4(FBN2):​c.952+10187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,122 control chromosomes in the GnomAD database, including 1,066 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 0.11 (1066 hom., cov: 32)
• Consequence: FBN2 NM_001999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN2	NM_001999.4	c.952+10187C>T		intron_variant		ENST00000262464.9
FBN2	XM_017009228.3	c.952+10187C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN2	ENST00000262464.9	c.952+10187C>T		intron_variant		1	NM_001999.4	P1
FBN2	ENST00000508053.6	c.952+10187C>T		intron_variant		5
FBN2	ENST00000508989.5	c.853+10187C>T		intron_variant		2
FBN2	ENST00000703787.1	n.659+10187C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16578 AN: 152004 Hom.: 1064 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.00674

Gnomad SAS AF: 0.0792

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.109 AC: 16590 AN: 152122 Hom.: 1066 Cov.: 32 AF XY: 0.108 AC XY: 8004 AN XY: 74384

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0688

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.00676

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0973

Gnomad4 NFE AF: 0.0945

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.0933 Hom.: 1154

Bravo AF: 0.108

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.75

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: rs1848501; hg19: chr5-127771987;