16-69373083-A-G

Position:

• chr16-69373083-A-G

Variant summary

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

The NM_005652.5(TERF2):​c.607-728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 151,940 control chromosomes in the GnomAD database, including 7,822 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 0.30 (7822 hom., cov: 31)
• Consequence: TERF2 NM_005652.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERF2	NM_005652.5	c.607-728T>C		intron_variant		ENST00000254942.8	NP_005643.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERF2	ENST00000254942.8	c.607-728T>C		intron_variant		1	NM_005652.5	ENSP00000254942	P1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46208 AN: 151822 Hom.: 7783 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.305 AC: 46305 AN: 151940 Hom.: 7822 Cov.: 31 AF XY: 0.301 AC XY: 22348 AN XY: 74278

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0996

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.306

Alfa AF: 0.265 Hom.: 2740

Bravo AF: 0.310

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0040
DANN	Benign	0.42

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: rs3785074; hg19: chr16-69406986;