16-69357811-C-G

Variant names:

• chr16-69357811-C-G
• rs9925619
• NM_005652.5:c.1427-250G>C

Variant summary

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

The NM_005652.5(TERF2):​c.1427-250G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 150,920 control chromosomes in the GnomAD database, including 7,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7472 hom., cov: 31)
• Consequence: TERF2 NM_005652.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0800
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-69357811-C-G is Benign according to our data. Variant chr16-69357811-C-G is described in ClinVar as Benign. ClinVar VariationId is 1228279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF2	NM_005652.5	MANE Select	c.1427-250G>C		intron	N/A	NP_005643.2	Q15554-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF2	ENST00000254942.8	TSL:1 MANE Select	c.1427-250G>C		intron	N/A	ENSP00000254942.3	Q15554-3
	TERF2	ENST00000903039.1		c.1427-253G>C		intron	N/A	ENSP00000573098.1
	TERF2	ENST00000966429.1		c.1424-250G>C		intron	N/A	ENSP00000636488.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45158 AN: 150814 Hom.: 7438 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.300 AC: 45250 AN: 150920 Hom.: 7472 Cov.: 31 AF XY: 0.296 AC XY: 21832 AN XY: 73660

African (AFR) AF: 0.409 AC: 16790 AN: 41004

American (AMR) AF: 0.255 AC: 3864 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3462

East Asian (EAS) AF: 0.0903 AC: 465 AN: 5150

South Asian (SAS) AF: 0.348 AC: 1670 AN: 4804

European-Finnish (FIN) AF: 0.188 AC: 1920 AN: 10222

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18642 AN: 67834

Other (OTH) AF: 0.304 AC: 639 AN: 2100

Alfa AF: 0.128 Hom.: 195

Bravo AF: 0.305

Asia WGS AF: 0.285 AC: 992 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.50
PhyloP100		0.080
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: rs9925619; hg19: chr16-69391714;