5-128310112-G-C

Variant names:

• chr5-128310112-G-C
• rs779999668
• NM_001999.4:c.5075-4C>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001999.4(FBN2):​c.5075-4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,456,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: FBN2 NM_001999.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001170
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.12

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-128310112-G-C is Benign according to our data. Variant chr5-128310112-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 458770.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.5075-4C>G		splice_region_variant, intron_variant	Intron 39 of 64	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.4922-4C>G		splice_region_variant, intron_variant	Intron 38 of 63		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.5075-4C>G		splice_region_variant, intron_variant	Intron 39 of 64	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000703783.1	n.1859-4C>G		splice_region_variant, intron_variant	Intron 14 of 37
FBN2	ENST00000703785.1	n.1778-4C>G		splice_region_variant, intron_variant	Intron 13 of 26

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251112 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad SAS 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: 0.00000412 AC: 6 AN: 1456016 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 724826

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital contractural arachnodactyly Benign:1

Feb 11, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.081
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.010		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: rs779999668; hg19: chr5-127645804;