2-32947681-C-T

Variant names:

• chr2-32947681-C-T
• rs202228164
• NM_206943.4:c.357C>T
• LTBP1 p.His119His

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_206943.4(LTBP1):​c.357C>T​(p.His119His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 1,342,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: LTBP1 NM_206943.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 1 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.302 with no splicing effect.

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.357C>T	p.His119His	synonymous	Exon 1 of 34	NP_996826.3	Q14766-1
	LTBP1	NM_001394905.1		c.357C>T	p.His119His	synonymous	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.357C>T	p.His119His	synonymous	Exon 1 of 34	ENSP00000386043.2	Q14766-1
	LTBP1	ENST00000929169.1		c.357C>T	p.His119His	synonymous	Exon 1 of 34	ENSP00000599228.1
	LTBP1	ENST00000954823.1		c.357C>T	p.His119His	synonymous	Exon 1 of 34	ENSP00000624882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000868 AC: 1 AN: 115158 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000182

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000223 AC: 3 AN: 1342892 Hom.: 0 Cov.: 33 AF XY: 0.00000301 AC XY: 2 AN XY: 664300

African (AFR) AF: 0.00 AC: 0 AN: 27338

American (AMR) AF: 0.00 AC: 0 AN: 30142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23320

East Asian (EAS) AF: 0.0000691 AC: 2 AN: 28958

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5202

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052918

Other (OTH) AF: 0.00 AC: 0 AN: 54898

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs202228164; hg19: chr2-33172748;