chr1-218346056-G-GCACACACACACA

Variant names:

• chr1-218346056-G-GCACACACACACA
• rs151329324
• NM_003238.6:c.-632_-621dupACACACACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003238.6(TGFB2):​c.-632_-621dupACACACACACAC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 145,590 control chromosomes in the GnomAD database, including 92 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_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: 𝑓 0.023 (92 hom., cov: 28)
• Consequence: TGFB2 NM_003238.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715
• Publications: 1 publications found

Genes affected

TGFB2 (HGNC:11768): (transforming growth factor beta 2) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers. A chromosomal translocation that includes this gene is associated with Peters' anomaly, a congenital defect of the anterior chamber of the eye. Mutations in this gene may be associated with Loeys-Dietz syndrome. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

TGFB2-AS1 (HGNC:50628): (TGFB2 antisense RNA 1 (head to head))

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003238.6. 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
	TGFB2	NM_003238.6	MANE Select	c.-632_-621dupACACACACACAC		5_prime_UTR	Exon 1 of 7	NP_003229.1	P61812-1
	TGFB2	NM_001135599.4		c.-632_-621dupACACACACACAC		5_prime_UTR	Exon 1 of 8	NP_001129071.1	P61812-2
	TGFB2	NR_138148.2		n.735_746dupACACACACACAC		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB2	ENST00000366930.9	TSL:1 MANE Select	c.-632_-621dupACACACACACAC		5_prime_UTR	Exon 1 of 7	ENSP00000355897.4	P61812-1
	TGFB2-AS1	ENST00000774588.1		n.239-680_239-669dupTGTGTGTGTGTG		intron	N/A
	TGFB2-AS1	ENST00000774589.1		n.32-680_32-669dupTGTGTGTGTGTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3359 AN: 145514 Hom.: 91 Cov.: 28

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0197

Gnomad EAS AF: 0.00485

Gnomad SAS AF: 0.000911

Gnomad FIN AF: 0.000933

Gnomad MID AF: 0.0195

Gnomad NFE AF: 0.00462

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0231 AC: 3365 AN: 145590 Hom.: 92 Cov.: 28 AF XY: 0.0234 AC XY: 1656 AN XY: 70902

African (AFR) AF: 0.0669 AC: 2651 AN: 39632

American (AMR) AF: 0.0180 AC: 265 AN: 14694

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 67 AN: 3396

East Asian (EAS) AF: 0.00487 AC: 23 AN: 4724

South Asian (SAS) AF: 0.00114 AC: 5 AN: 4392

European-Finnish (FIN) AF: 0.000933 AC: 9 AN: 9648

Middle Eastern (MID) AF: 0.0213 AC: 6 AN: 282

European-Non Finnish (NFE) AF: 0.00462 AC: 305 AN: 65950

Other (OTH) AF: 0.0170 AC: 34 AN: 1996

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.71

Splicing

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

Other links and lift over

dbSNP: rs151329324; hg19: chr1-218519398;