NM_003238.6:c.-677T>C

Variant names:

• chr1-218346025-T-C
• rs112369231
• NM_003238.6:c.-677T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003238.6(TGFB2):​c.-677T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 150,444 control chromosomes in the GnomAD database, including 13,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.39 (13242 hom., cov: 28)
• Consequence: TGFB2 NM_003238.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.257
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-218346025-T-C is Benign according to our data. Variant chr1-218346025-T-C is described in ClinVar as Benign. ClinVar VariationId is 295468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 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.-677T>C		5_prime_UTR	Exon 1 of 7	NP_003229.1	P61812-1
	TGFB2	NM_001135599.4		c.-677T>C		5_prime_UTR	Exon 1 of 8	NP_001129071.1	P61812-2
	TGFB2	NR_138148.2		n.690T>C		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.-677T>C		5_prime_UTR	Exon 1 of 7	ENSP00000355897.4	P61812-1
	TGFB2-AS1	ENST00000414452.3	TSL:3	n.26A>G		non_coding_transcript_exon	Exon 1 of 3
	TGFB2-AS1	ENST00000689961.3		n.18A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.385 AC: 57841 AN: 150336 Hom.: 13210 Cov.: 28

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.337

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.385 AC: 57932 AN: 150444 Hom.: 13242 Cov.: 28 AF XY: 0.383 AC XY: 28142 AN XY: 73460

African (AFR) AF: 0.646 AC: 26304 AN: 40732

American (AMR) AF: 0.297 AC: 4510 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1093 AN: 3460

East Asian (EAS) AF: 0.377 AC: 1866 AN: 4954

South Asian (SAS) AF: 0.348 AC: 1652 AN: 4752

European-Finnish (FIN) AF: 0.312 AC: 3248 AN: 10426

Middle Eastern (MID) AF: 0.359 AC: 104 AN: 290

European-Non Finnish (NFE) AF: 0.268 AC: 18112 AN: 67626

Other (OTH) AF: 0.351 AC: 737 AN: 2098

Alfa AF: 0.329 Hom.: 1197

Bravo AF: 0.399

Asia WGS AF: 0.364 AC: 1263 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Loeys-Dietz syndrome 4 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Benign	0.67
PhyloP100		0.26
PromoterAI		0.096	Neutral

Splicing

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

Other links and lift over

dbSNP: rs112369231; hg19: chr1-218519367;