16-69374012-C-T

Variant names:

• chr16-69374012-C-T
• rs166134
• NM_005652.5:c.607-1657G>A

Variant summary

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

The NM_005652.5(TERF2):​c.607-1657G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 152,324 control chromosomes in the GnomAD database, including 74,159 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 0.99 (74159 hom., cov: 31)
• Consequence: TERF2 NM_005652.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF2	NM_005652.5	c.607-1657G>A		intron_variant	Intron 3 of 9	ENST00000254942.8	NP_005643.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF2	ENST00000254942.8	c.607-1657G>A		intron_variant	Intron 3 of 9	1	NM_005652.5	ENSP00000254942.3

Frequencies

GnomAD3 genomes AF: 0.987 AC: 150178 AN: 152206 Hom.: 74100 Cov.: 31

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.979

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.989

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

GnomAD4 genome AF: 0.987 AC: 150296 AN: 152324 Hom.: 74159 Cov.: 31 AF XY: 0.988 AC XY: 73561 AN XY: 74484

African (AFR) AF: 0.996 AC: 41395 AN: 41556

American (AMR) AF: 0.992 AC: 15176 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3433 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.998 AC: 4808 AN: 4820

European-Finnish (FIN) AF: 0.979 AC: 10403 AN: 10622

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.979 AC: 66618 AN: 68048

Other (OTH) AF: 0.989 AC: 2091 AN: 2114

Alfa AF: 0.979 Hom.: 33735

Bravo AF: 0.987

Asia WGS AF: 0.998 AC: 3472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.49
DANN	Benign	0.58
PhyloP100		0.35
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: rs166134; hg19: chr16-69407915;