rs6982126

Variant names:

• chr8-73027388-C-T
• rs6982126
• NM_017489.3:c.887+336C>T

Variant summary

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

The NM_017489.3(TERF1):​c.887+336C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,022 control chromosomes in the GnomAD database, including 4,770 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 0.25 (4770 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 8 publications found

Genes affected

TERF1 (HGNC:11728): (telomeric repeat binding factor 1) This gene encodes a telomere specific protein which is a component of the telomere nucleoprotein complex. This protein is present at telomeres throughout the cell cycle and functions as an inhibitor of telomerase, acting in cis to limit the elongation of individual chromosome ends. The protein structure contains a C-terminal Myb motif, a dimerization domain near its N-terminus and an acidic N-terminus. Multiple transcripts of this gene are alternatively spliced products. [provided by RefSeq, Aug 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.887+336C>T		intron_variant	Intron 6 of 9	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.887+336C>T		intron_variant	Intron 6 of 9	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37469 AN: 151904 Hom.: 4760 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.247 AC: 37510 AN: 152022 Hom.: 4770 Cov.: 32 AF XY: 0.243 AC XY: 18056 AN XY: 74344

African (AFR) AF: 0.294 AC: 12181 AN: 41440

American (AMR) AF: 0.194 AC: 2965 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3468

East Asian (EAS) AF: 0.175 AC: 907 AN: 5172

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4826

European-Finnish (FIN) AF: 0.185 AC: 1957 AN: 10584

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16467 AN: 67962

Other (OTH) AF: 0.256 AC: 538 AN: 2104

Alfa AF: 0.245 Hom.: 19606

Bravo AF: 0.246

Asia WGS AF: 0.215 AC: 748 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.69
PhyloP100		0.39
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: rs6982126; hg19: chr8-73939623;