rs538338631

Variant names:

• chr2-32947621-ACCGCCGCCGCCG-A
• rs538338631
• NM_206943.4:c.307_318delCCGCCGCCGCCG

Your query was ambiguous. Multiple possible variants found:

• chr2-32947621-ACCGCCGCCGCCG-A
• chr2-32947621-ACCGCCGCCGCCG-ACCG
• chr2-32947621-ACCGCCGCCGCCG-ACCGCCG
• chr2-32947621-ACCGCCGCCGCCG-ACCGCCGCCG
• chr2-32947621-ACCGCCGCCGCCG-ACCGCCGCCGCCGCCG
• chr2-32947621-ACCGCCGCCGCCG-ACCGCCGCCGCCGCCGCCG
• chr2-32947621-ACCGCCGCCGCCG-ACCGCCGCCGCCGCCGCCGCCG
• chr2-32947621-ACCGCCGCCGCCG-ACCGCCGCCGCCGCCGCCGCCGCCG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_206943.4(LTBP1):​c.307_318delCCGCCGCCGCCG​(p.Pro103_Pro106del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000255 in 1,176,626 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: LTBP1 NM_206943.4 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 0 publications found

Genes affected

LTBP1 (HGNC:6714): (latent transforming growth factor beta binding protein 1) The protein encoded by this gene belongs to the family of latent TGF-beta binding proteins (LTBPs). The secretion and activation of TGF-betas is regulated by their association with latency-associated proteins and with latent TGF-beta binding proteins. The product of this gene targets latent complexes of transforming growth factor beta to the extracellular matrix, where the latent cytokine is subsequently activated by several different mechanisms. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

LTBP1 Gene-Disease associations (from GenCC):

• cutis laxa, autosomal recessive, type 2E

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_206943.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	NM_206943.4	MANE Select	c.307_318delCCGCCGCCGCCG	p.Pro103_Pro106del	conservative_inframe_deletion	Exon 1 of 34	NP_996826.3	Q14766-1
	LTBP1	NM_001394905.1		c.307_318delCCGCCGCCGCCG	p.Pro103_Pro106del	conservative_inframe_deletion	Exon 1 of 34	NP_001381834.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTBP1	ENST00000404816.7	TSL:5 MANE Select	c.307_318delCCGCCGCCGCCG	p.Pro103_Pro106del	conservative_inframe_deletion	Exon 1 of 34	ENSP00000386043.2	Q14766-1
	LTBP1	ENST00000929169.1		c.307_318delCCGCCGCCGCCG	p.Pro103_Pro106del	conservative_inframe_deletion	Exon 1 of 34	ENSP00000599228.1
	LTBP1	ENST00000954823.1		c.307_318delCCGCCGCCGCCG	p.Pro103_Pro106del	conservative_inframe_deletion	Exon 1 of 34	ENSP00000624882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000255 AC: 3 AN: 1176626 Hom.: 0 AF XY: 0.00000523 AC XY: 3 AN XY: 573438

African (AFR) AF: 0.00 AC: 0 AN: 23190

American (AMR) AF: 0.00 AC: 0 AN: 9590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15408

East Asian (EAS) AF: 0.00 AC: 0 AN: 25208

South Asian (SAS) AF: 0.0000222 AC: 1 AN: 45112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3448

European-Non Finnish (NFE) AF: 0.00000205 AC: 2 AN: 974962

Other (OTH) AF: 0.00 AC: 0 AN: 47408

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

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

Other links and lift over

dbSNP: rs538338631; hg19: chr2-33172688;