rs2929586

Variant names:

• chr8-73013177-G-A
• rs2929586
• NM_017489.3:c.320-718G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017489.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	NM_017489.3	MANE Select	c.320-718G>A		intron	N/A	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.320-718G>A		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.320-718G>A		intron	N/A	NP_001397857.1	A0A7I2YQE7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	ENST00000276603.10	TSL:1 MANE Select	c.320-718G>A		intron	N/A	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.320-718G>A		intron	N/A	ENSP00000276602.6	P54274-2
	TERF1	ENST00000899325.1		c.320-718G>A		intron	N/A	ENSP00000569384.1

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

African (AFR) AF: 0.744 AC: 30869 AN: 41508

American (AMR) AF: 0.528 AC: 8069 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2421 AN: 3472

East Asian (EAS) AF: 0.320 AC: 1656 AN: 5168

South Asian (SAS) AF: 0.591 AC: 2848 AN: 4820

European-Finnish (FIN) AF: 0.697 AC: 7371 AN: 10570

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47646 AN: 67968

Other (OTH) AF: 0.688 AC: 1449 AN: 2106

Alfa AF: 0.665 Hom.: 11676

Bravo AF: 0.665

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.24
PhyloP100		0.18
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: rs2929586; hg19: chr8-73925412;