rs6989159

Positions:

• chr8-73023548-A-G

Variant summary

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

The NM_017489.3(TERF1):​c.624+1246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 152,118 control chromosomes in the GnomAD database, including 190 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 0.035 (190 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERF1	NM_017489.3	c.624+1246A>G		intron_variant		ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.624+1246A>G		intron_variant		1	NM_017489.3	ENSP00000276603	P4

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5286 AN: 152000 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00737

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0349 AC: 5308 AN: 152118 Hom.: 190 Cov.: 32 AF XY: 0.0352 AC XY: 2619 AN XY: 74370

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0222

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0263

Gnomad4 NFE AF: 0.00737

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0281 Hom.: 16

Bravo AF: 0.0354

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6989159; hg19: chr8-73935783;