11-65539063-GGGCGGCGTC-GGGCGGCGTCGGCGGCGTC

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001130144.3(LTBP3):​c.*8_*16dupGACGCCGCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,364,480 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (6 hom.)
• Consequence: LTBP3 NM_001130144.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00268 (408/152112) while in subpopulation SAS AF= 0.00393 (19/4834). AF 95% confidence interval is 0.00326. There are 0 homozygotes in gnomad4. There are 198 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP3	NM_001130144.3	c.*8_*16dupGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	ENST00000301873.11	NP_001123616.1
LTBP3	NM_021070.4	c.*8_*16dupGACGCCGCC		3_prime_UTR_variant	Exon 27 of 27		NP_066548.2
LTBP3	NM_001164266.1	c.*8_*16dupGACGCCGCC		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_*16dupGACGCCGCC		3_prime_UTR_variant	Exon 28 of 28	2	NM_001130144.3	ENSP00000301873.5

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 408 AN: 152002 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.000284

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.000302 AC: 11 AN: 36384 Hom.: 0 AF XY: 0.000325 AC XY: 7 AN XY: 21538

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000178

Gnomad FIN exome AF: 0.000402

Gnomad NFE exome AF: 0.000509

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00286 AC: 3467 AN: 1212368 Hom.: 6 Cov.: 31 AF XY: 0.00271 AC XY: 1599 AN XY: 589236

Gnomad4 AFR exome AF: 0.000737

Gnomad4 AMR exome AF: 0.000964

Gnomad4 ASJ exome AF: 0.00372

Gnomad4 EAS exome AF: 0.00154

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.000738

Gnomad4 NFE exome AF: 0.00313

Gnomad4 OTH exome AF: 0.00250

GnomAD4 genome AF: 0.00268 AC: 408 AN: 152112 Hom.: 0 Cov.: 33 AF XY: 0.00266 AC XY: 198 AN XY: 74378

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00223

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.000284

Gnomad4 NFE AF: 0.00363

Gnomad4 OTH AF: 0.00427

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

Not reported in ClinVar

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;