16-69385180-T-A

Variant names:

• chr16-69385180-T-A
• rs8061382
• NM_005652.5:c.475+211A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.79).
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4278 AD gene.

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.475+211A>T		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.475+211A>T		intron	N/A	ENSP00000254942.3
	TERF2	ENST00000567296.6	TSL:1	c.475+211A>T		intron	N/A	ENSP00000454955.2
	TERF2	ENST00000566750.5	TSL:2	c.112+211A>T		intron	N/A	ENSP00000456022.1

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

African (AFR) AF: 0.0232 AC: 962 AN: 41438

American (AMR) AF: 0.0379 AC: 578 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 32 AN: 3468

East Asian (EAS) AF: 0.0138 AC: 71 AN: 5150

South Asian (SAS) AF: 0.0163 AC: 78 AN: 4798

European-Finnish (FIN) AF: 0.0291 AC: 306 AN: 10522

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0318 AC: 2163 AN: 67956

Other (OTH) AF: 0.0257 AC: 54 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.84
PhyloP100		-0.29
PromoterAI		-0.0024	Neutral
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: rs8061382; hg19: chr16-69419083;