rs10482718

Variant names:

• chr1-218345400-A-G
• rs10482718
• NM_003238.6:c.-1302A>G

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.-1302A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 152,408 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (96 hom., cov: 32)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: TGFB2 NM_003238.6 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.377
• Publications: 2 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=-0.85).
• BP6: Variant 1-218345400-A-G is Benign according to our data. Variant chr1-218345400-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 295455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0735 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.-1302A>G		5_prime_UTR	Exon 1 of 7	NP_003229.1	P61812-1
	TGFB2	NM_001135599.4		c.-1302A>G		5_prime_UTR	Exon 1 of 8	NP_001129071.1	P61812-2
	TGFB2	NR_138148.2		n.65A>G		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.-1302A>G		5_prime_UTR	Exon 1 of 7	ENSP00000355897.4	P61812-1
	TGFB2-AS1	ENST00000687392.2		n.588T>C		non_coding_transcript_exon	Exon 1 of 1
	TGFB2-AS1	ENST00000774611.1		n.19T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4651 AN: 152186 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.0798

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0288 AC: 3 AN: 104 Hom.: 0 Cov.: 0 AF XY: 0.0263 AC XY: 2 AN XY: 76

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0417 AC: 3 AN: 72

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0305 AC: 4652 AN: 152304 Hom.: 96 Cov.: 32 AF XY: 0.0292 AC XY: 2173 AN XY: 74470

African (AFR) AF: 0.0234 AC: 972 AN: 41558

American (AMR) AF: 0.0240 AC: 367 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3472

East Asian (EAS) AF: 0.0798 AC: 413 AN: 5174

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4822

European-Finnish (FIN) AF: 0.0219 AC: 233 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0360 AC: 2450 AN: 68038

Other (OTH) AF: 0.0321 AC: 68 AN: 2116

Alfa AF: 0.0330 Hom.: 51

Bravo AF: 0.0321

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Loeys-Dietz syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.6
DANN	Benign	0.72
PhyloP100		0.38
PromoterAI		0.029	Neutral

Splicing

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

Other links and lift over

dbSNP: rs10482718; hg19: chr1-218518742;