rs153045

Positions:

• chr16-69363490-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005652.5(TERF2):​c.1341-2001A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,050 control chromosomes in the GnomAD database, including 7,223 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7223 hom., cov: 32)
• Consequence: TERF2 NM_005652.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

Genes affected

TERF2 (HGNC:11729): (telomeric repeat binding factor 2) This gene encodes a telomere specific protein, TERF2, which is a component of the telomere nucleoprotein complex. This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length and plays a key role in the protective activity of telomeres. While having similar telomere binding activity and domain organization, TERF2 differs from TERF1 in that its N terminus is basic rather than acidic. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERF2	NM_005652.5	c.1341-2001A>G		intron_variant		ENST00000254942.8	NP_005643.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERF2	ENST00000254942.8	c.1341-2001A>G		intron_variant		1	NM_005652.5	ENSP00000254942	P1
TERF2	ENST00000567130.1	n.179-2001A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42995 AN: 151932 Hom.: 7227 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.283 AC: 42975 AN: 152050 Hom.: 7223 Cov.: 32 AF XY: 0.289 AC XY: 21499 AN XY: 74292

Gnomad4 AFR AF: 0.0956

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.301

Alfa AF: 0.322 Hom.: 5519

Bravo AF: 0.271

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.67
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs153045; hg19: chr16-69397393;