rs862034

Positions:

• chr14-74524043-A-G
• chr14-74524043-A-T

Variant summary

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

The NM_000428.3(LTBP2):​c.2530+1081T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,900 control chromosomes in the GnomAD database, including 31,859 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 0.65 (31859 hom., cov: 31)
• Consequence: LTBP2 NM_000428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

Genes affected

LTBP2 (HGNC:6715): (latent transforming growth factor beta binding protein 2) The protein encoded by this gene belongs to the family of latent transforming growth factor (TGF)-beta binding proteins (LTBP), which are extracellular matrix proteins with multi-domain structure. This protein is the largest member of the LTBP family possessing unique regions and with most similarity to the fibrillins. It has thus been suggested that it may have multiple functions: as a member of the TGF-beta latent complex, as a structural component of microfibrils, and a role in cell adhesion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP2	NM_000428.3	c.2530+1081T>C		intron_variant		ENST00000261978.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP2	ENST00000261978.9	c.2530+1081T>C		intron_variant		1	NM_000428.3	P1
LTBP2	ENST00000556690.5	c.2530+1081T>C		intron_variant		5
LTBP2	ENST00000553939.5	c.2530+1081T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98137 AN: 151780 Hom.: 31819 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.647 AC: 98229 AN: 151900 Hom.: 31859 Cov.: 31 AF XY: 0.645 AC XY: 47900 AN XY: 74236

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.636

Alfa AF: 0.632 Hom.: 36326

Bravo AF: 0.650

Asia WGS AF: 0.675 AC: 2350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.92

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: rs862034; hg19: chr14-74990746;