8-73039667-A-G

Variant names:

• chr8-73039667-A-G
• rs2306492
• NM_017489.3:c.1143+448A>G

Variant summary

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

The NM_017489.3(TERF1):​c.1143+448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,866 control chromosomes in the GnomAD database, including 27,631 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 0.59 (27631 hom., cov: 31)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.1143+448A>G		intron_variant	Intron 9 of 9	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.1143+448A>G		intron_variant	Intron 9 of 9	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89762 AN: 151748 Hom.: 27641 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.591 AC: 89785 AN: 151866 Hom.: 27631 Cov.: 31 AF XY: 0.587 AC XY: 43523 AN XY: 74200

African (AFR) AF: 0.468 AC: 19346 AN: 41368

American (AMR) AF: 0.496 AC: 7563 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2412 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1543 AN: 5146

South Asian (SAS) AF: 0.577 AC: 2777 AN: 4816

European-Finnish (FIN) AF: 0.670 AC: 7061 AN: 10538

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47089 AN: 67960

Other (OTH) AF: 0.614 AC: 1294 AN: 2108

Alfa AF: 0.635 Hom.: 9247

Bravo AF: 0.571

Asia WGS AF: 0.468 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.84
DANN	Benign	0.66
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2306492; hg19: chr8-73951902;