chr1-218442672-C-T

Variant names:

• chr1-218442672-C-T
• rs1418556
• NM_003238.6:c.*1310C>T

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.*1310C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 150,078 control chromosomes in the GnomAD database, including 11,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11279 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGFB2 NM_003238.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.600
• Publications: 10 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-OT1 (HGNC:50629): (TGFB2 overlapping transcript 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-218442672-C-T is Benign according to our data. Variant chr1-218442672-C-T is described in ClinVar as Benign. ClinVar VariationId is 295514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 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.*1310C>T		3_prime_UTR	Exon 7 of 7	NP_003229.1	P61812-1
	TGFB2	NM_001135599.4		c.*1310C>T		3_prime_UTR	Exon 8 of 8	NP_001129071.1	P61812-2
	TGFB2-OT1	NR_125715.1		n.47C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFB2	ENST00000366930.9	TSL:1 MANE Select	c.*1310C>T		3_prime_UTR	Exon 7 of 7	ENSP00000355897.4	P61812-1
	TGFB2	ENST00000366929.4	TSL:1	c.*1310C>T		3_prime_UTR	Exon 8 of 8	ENSP00000355896.4	P61812-2
	TGFB2-OT1	ENST00000625474.1	TSL:6	n.47C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 55944 AN: 149984 Hom.: 11264 Cov.: 30

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.367

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.373 AC: 55991 AN: 150078 Hom.: 11279 Cov.: 30 AF XY: 0.378 AC XY: 27666 AN XY: 73178

African (AFR) AF: 0.464 AC: 18978 AN: 40888

American (AMR) AF: 0.470 AC: 7084 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1118 AN: 3454

East Asian (EAS) AF: 0.716 AC: 3646 AN: 5094

South Asian (SAS) AF: 0.370 AC: 1761 AN: 4764

European-Finnish (FIN) AF: 0.306 AC: 3073 AN: 10046

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19134 AN: 67484

Other (OTH) AF: 0.370 AC: 774 AN: 2094

Alfa AF: 0.309 Hom.: 1576

Bravo AF: 0.394

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	-0.91
CADD	Benign	0.69
DANN	Benign	0.32
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1418556; hg19: chr1-218616014;