16-69373083-A-G

Variant names:

• chr16-69373083-A-G
• rs3785074
• NM_005652.5:c.607-728T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 44 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005652.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF2	NM_005652.5	MANE Select	c.607-728T>C		intron	N/A	NP_005643.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF2	ENST00000254942.8	TSL:1 MANE Select	c.607-728T>C		intron	N/A	ENSP00000254942.3
	TERF2	ENST00000567296.6	TSL:1	c.607-728T>C		intron	N/A	ENSP00000454955.2
	TERF2	ENST00000566750.5	TSL:2	c.244-728T>C		intron	N/A	ENSP00000456022.1

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

African (AFR) AF: 0.424 AC: 17566 AN: 41406

American (AMR) AF: 0.258 AC: 3936 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 841 AN: 3464

East Asian (EAS) AF: 0.0996 AC: 514 AN: 5162

South Asian (SAS) AF: 0.344 AC: 1658 AN: 4816

European-Finnish (FIN) AF: 0.195 AC: 2055 AN: 10562

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18671 AN: 67964

Other (OTH) AF: 0.306 AC: 645 AN: 2110

Alfa AF: 0.269 Hom.: 3125

Bravo AF: 0.310

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0040
DANN	Benign	0.42
PhyloP100		-3.1
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: rs3785074; hg19: chr16-69406986;