chr1-218346056-GCACA-G

Variant names:

• chr1-218346056-GCACA-G
• rs151329324
• NM_003238.6:c.-624_-621delACAC

Variant summary

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

The NM_003238.6(TGFB2):​c.-624_-621delACAC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 145,656 control chromosomes in the GnomAD database, including 10 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.010 (10 hom., cov: 28)
• Consequence: TGFB2 NM_003238.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0102 (1489/145656) while in subpopulation EAS AF= 0.036 (170/4720). AF 95% confidence interval is 0.0316. There are 10 homozygotes in gnomad4. There are 737 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1489 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFB2	NM_003238.6	c.-624_-621delACAC		5_prime_UTR_variant	Exon 1 of 7	ENST00000366930.9	NP_003229.1
TGFB2	NM_001135599.4	c.-624_-621delACAC		5_prime_UTR_variant	Exon 1 of 8		NP_001129071.1
TGFB2	NR_138148.2	n.743_746delACAC		non_coding_transcript_exon_variant	Exon 1 of 7
TGFB2	NR_138149.2	n.743_746delACAC		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFB2	ENST00000366930	c.-624_-621delACAC		5_prime_UTR_variant	Exon 1 of 7	1	NM_003238.6	ENSP00000355897.4

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1492 AN: 145578 Hom.: 10 Cov.: 28

Gnomad AFR AF: 0.00886

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00456

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0390

Gnomad NFE AF: 0.00929

Gnomad OTH AF: 0.0131

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

GnomAD4 genome AF: 0.0102 AC: 1489 AN: 145656 Hom.: 10 Cov.: 28 AF XY: 0.0104 AC XY: 737 AN XY: 70944

Gnomad4 AFR AF: 0.00884

Gnomad4 AMR AF: 0.00456

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.0360

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.00929

Gnomad4 OTH AF: 0.0130

Bravo AF: 0.00969

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: rs151329324; hg19: chr1-218519398;