rs539110133

Variant names:

• chr11-65539063-GGGCGGCGTC-G
• rs539110133
• NM_001130144.3:c.*8_*16delGACGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr11-65539063-GGGCGGCGTC-G
• chr11-65539063-GGGCGGCGTC-GGGCGGCGTCGGCGGCGTC
• chr11-65539063-GGGCGGCGTC-GGGCGGCGTCGGCGGCGTCGGCGGCGTC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001130144.3(LTBP3):​c.*8_*16delGACGCCGCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,364,696 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00046 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (4 hom.)
• Consequence: LTBP3 NM_001130144.3 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.81

Genes affected

LTBP3 (HGNC:6716): (latent transforming growth factor beta binding protein 3) The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 11-65539063-GGGCGGCGTC-G is Benign according to our data. Variant chr11-65539063-GGGCGGCGTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3043750.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.*8_*16delGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.*8_*16delGACGCCGCC		3_prime_UTR_variant	Exon 27 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.*8_*16delGACGCCGCC		3_prime_UTR_variant	Exon 27 of 27		NP_001157738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP3	ENST00000301873	c.*8_*16delGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes AF: 0.000461 AC: 70 AN: 152008 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000742 AC: 27 AN: 36384 Hom.: 2 AF XY: 0.000604 AC XY: 13 AN XY: 21538

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000178

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000936

GnomAD4 exome AF: 0.000562 AC: 682 AN: 1212688 Hom.: 4 AF XY: 0.000517 AC XY: 305 AN XY: 589414

Gnomad4 AFR exome AF: 0.000173

Gnomad4 AMR exome AF: 0.000803

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000226

Gnomad4 FIN exome AF: 0.0000671

Gnomad4 NFE exome AF: 0.000632

Gnomad4 OTH exome AF: 0.000512

GnomAD4 genome AF: 0.000461 AC: 70 AN: 152008 Hom.: 1 Cov.: 33 AF XY: 0.000323 AC XY: 24 AN XY: 74262

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000413

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000163 Hom.: 0

Bravo AF: 0.000446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

LTBP3-related disorder Benign:1

Dec 16, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs539110133; hg19: chr11-65306534;