5-128538114-C-T

Variant names:

• chr5-128538114-C-T
• rs7712942
• NM_001999.4:c.-511G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001999.4(FBN2):​c.-511G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 157,096 control chromosomes in the GnomAD database, including 18,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (18624 hom., cov: 32)
  • Exomes 𝑓: 0.34 (323 hom.)
• Consequence: FBN2 NM_001999.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.305

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]

SLC27A6 (HGNC:11000): (solute carrier family 27 member 6) This gene encodes a member of the fatty acid transport protein family (FATP). FATPs are involved in the uptake of long-chain fatty acids and have unique expression patterns. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-128538114-C-T is Benign according to our data. Variant chr5-128538114-C-T is described in ClinVar as [Benign]. Clinvar id is 675097.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.-511G>A		5_prime_UTR_variant	Exon 1 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.-511G>A		5_prime_UTR_variant	Exon 1 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.-511G>A		5_prime_UTR_variant	Exon 1 of 65	1	NM_001999.4	ENSP00000262464.4

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66574 AN: 151834 Hom.: 18584 Cov.: 32

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.335 AC: 1727 AN: 5152 Hom.: 323 Cov.: 0 AF XY: 0.329 AC XY: 921 AN XY: 2796

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.439 AC: 66671 AN: 151944 Hom.: 18624 Cov.: 32 AF XY: 0.431 AC XY: 32021 AN XY: 74252

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.392

Alfa AF: 0.383 Hom.: 1745

Bravo AF: 0.453

Asia WGS AF: 0.351 AC: 1219 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.61

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: rs7712942; hg19: chr5-127873807; COSMIC: COSV52502807; COSMIC: COSV52502807;