1-218345988-A-C

Variant names:

• chr1-218345988-A-C
• rs73110310
• NM_003238.6:c.-714A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003238.6(TGFB2):​c.-714A>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 0.101 in 151,162 control chromosomes in the GnomAD database, including 1,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1569 hom., cov: 30)
• Consequence: TGFB2 NM_003238.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.389
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-218345988-A-C is Benign according to our data. Variant chr1-218345988-A-C is described in ClinVar as Benign. ClinVar VariationId is 295463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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.-714A>C		5_prime_UTR	Exon 1 of 7	NP_003229.1	P61812-1
	TGFB2	NM_001135599.4		c.-714A>C		5_prime_UTR	Exon 1 of 8	NP_001129071.1	P61812-2
	TGFB2	NR_138148.2		n.653A>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.-714A>C		5_prime_UTR	Exon 1 of 7	ENSP00000355897.4	P61812-1
	TGFB2-AS1	ENST00000414452.3	TSL:3	n.63T>G		non_coding_transcript_exon	Exon 1 of 3
	TGFB2-AS1	ENST00000689961.3		n.55T>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15234 AN: 151044 Hom.: 1556 Cov.: 30

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0299

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.0803

Gnomad SAS AF: 0.0115

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0449

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.101 AC: 15284 AN: 151162 Hom.: 1569 Cov.: 30 AF XY: 0.0981 AC XY: 7242 AN XY: 73856

African (AFR) AF: 0.266 AC: 10923 AN: 41020

American (AMR) AF: 0.0535 AC: 816 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.0803 AC: 402 AN: 5008

South Asian (SAS) AF: 0.0117 AC: 56 AN: 4794

European-Finnish (FIN) AF: 0.0219 AC: 231 AN: 10554

Middle Eastern (MID) AF: 0.0517 AC: 15 AN: 290

European-Non Finnish (NFE) AF: 0.0370 AC: 2505 AN: 67762

Other (OTH) AF: 0.0771 AC: 162 AN: 2102

Alfa AF: 0.0458 Hom.: 375

Bravo AF: 0.113

Asia WGS AF: 0.0440 AC: 152 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Loeys-Dietz syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.56
PhyloP100		-0.39
PromoterAI		0.025	Neutral

Splicing

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

Other links and lift over

dbSNP: rs73110310; hg19: chr1-218519330;