rs2929586

Positions:

• chr8-73013177-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017489.3(TERF1):​c.320-718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,090 control chromosomes in the GnomAD database, including 35,641 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 0.68 (35641 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF1	NM_017489.3	c.320-718G>A		intron_variant		ENST00000276603.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF1	ENST00000276603.10	c.320-718G>A		intron_variant		1	NM_017489.3	P4

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102947 AN: 151972 Hom.: 35614 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.677 AC: 103032 AN: 152090 Hom.: 35641 Cov.: 32 AF XY: 0.672 AC XY: 49927 AN XY: 74336

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.688

Alfa AF: 0.674 Hom.: 5975

Bravo AF: 0.665

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.24

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: rs2929586; hg19: chr8-73925412;