rs8061382

chr16-69385180-T-Achr16-69385180-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005652.5(TERF2):c.475+211A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 151,882 control chromosomes in the GnomAD database, including 91 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 0.028 (91 hom., cov: 31)
• Consequence: TERF2 NM_005652.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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=-0.79).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0282 (4278/151882) while in subpopulation AMR AF= 0.0379 (578/15242). AF 95% confidence interval is 0.0354. There are 91 homozygotes in gnomad4. There are 2085 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 4272 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF2	NM_005652.5	c.475+211A>T		intron_variant		ENST00000254942.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF2	ENST00000254942.8	c.475+211A>T		intron_variant		1	NM_005652.5	P1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4272 AN: 151764 Hom.: 91 Cov.: 31

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0255

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

GnomAD4 genome AF: 0.0282 AC: 4278 AN: 151882 Hom.: 91 Cov.: 31 AF XY: 0.0281 AC XY: 2085 AN XY: 74212

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.00923

Gnomad4 EAS AF: 0.0138

Gnomad4 SAS AF: 0.0163

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.0318

Gnomad4 OTH AF: 0.0257

Alfa AF: 0.0103 Hom.: 2

Bravo AF: 0.0276

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.5
Dann	Benign	0.84

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: rs8061382; hg19: chr16-69419083;