rs2306494

Positions:

• chr8-73038992-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017489.3(TERF1):​c.1040-124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 831,048 control chromosomes in the GnomAD database, including 178,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27861 hom., cov: 32)
  • Exomes 𝑓: 0.66 (151062 hom.)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.349

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 8-73038992-G-A is Benign according to our data. Variant chr8-73038992-G-A is described in ClinVar as [Benign]. Clinvar id is 1294451.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.1040-124G>A		intron_variant		ENST00000276603.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF1	ENST00000276603.10	c.1040-124G>A		intron_variant		1	NM_017489.3	P4

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90327 AN: 151842 Hom.: 27870 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.658 AC: 447082 AN: 679088 Hom.: 151062 AF XY: 0.656 AC XY: 226758 AN XY: 345668

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.479

Gnomad4 ASJ exome AF: 0.714

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.662

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.595 AC: 90356 AN: 151960 Hom.: 27861 Cov.: 32 AF XY: 0.591 AC XY: 43864 AN XY: 74278

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.620

Alfa AF: 0.658 Hom.: 11915

Bravo AF: 0.575

Asia WGS AF: 0.470 AC: 1626 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.37

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: rs2306494; hg19: chr8-73951227;