rs153045

Variant names:

• chr16-69363490-T-C
• rs153045
• NM_005652.5:c.1341-2001A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005652.5(TERF2):​c.1341-2001A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,050 control chromosomes in the GnomAD database, including 7,223 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 0.28 (7223 hom., cov: 32)
• Consequence: TERF2 NM_005652.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 16 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF2	NM_005652.5	c.1341-2001A>G		intron_variant	Intron 7 of 9	ENST00000254942.8	NP_005643.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF2	ENST00000254942.8	c.1341-2001A>G		intron_variant	Intron 7 of 9	1	NM_005652.5	ENSP00000254942.3
TERF2	ENST00000567130.1	n.179-2001A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42995 AN: 151932 Hom.: 7227 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.283 AC: 42975 AN: 152050 Hom.: 7223 Cov.: 32 AF XY: 0.289 AC XY: 21499 AN XY: 74292

African (AFR) AF: 0.0956 AC: 3971 AN: 41522

American (AMR) AF: 0.346 AC: 5283 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3468

East Asian (EAS) AF: 0.422 AC: 2175 AN: 5148

South Asian (SAS) AF: 0.354 AC: 1704 AN: 4814

European-Finnish (FIN) AF: 0.445 AC: 4684 AN: 10534

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22984 AN: 67974

Other (OTH) AF: 0.301 AC: 636 AN: 2116

Alfa AF: 0.312 Hom.: 8602

Bravo AF: 0.271

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.67
DANN	Benign	0.69
PhyloP100		-0.43
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: rs153045; hg19: chr16-69397393;