8-73039667-A-G

Position:

• chr8-73039667-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.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

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=-0.95).
• 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/exons	MANE	UniProt
TERF1	NM_017489.3	c.1143+448A>G		intron_variant		ENST00000276603.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF1	ENST00000276603.10	c.1143+448A>G		intron_variant		1	NM_017489.3	P4

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

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.614

Alfa AF: 0.617 Hom.: 4558

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2306492; hg19: chr8-73951902;