8-73030477-C-T

Position:

• chr8-73030477-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017489.3(TERF1):​c.947+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 796,956 control chromosomes in the GnomAD database, including 19,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3129 hom., cov: 32)
  • Exomes 𝑓: 0.22 (16709 hom.)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.965

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 8-73030477-C-T is Benign according to our data. Variant chr8-73030477-C-T is described in ClinVar as [Benign]. Clinvar id is 1268267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF1	NM_017489.3	c.947+82C>T		intron_variant		ENST00000276603.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF1	ENST00000276603.10	c.947+82C>T		intron_variant		1	NM_017489.3	P4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30301 AN: 151980 Hom.: 3129 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.221 AC: 142452 AN: 644858 Hom.: 16709 Cov.: 9 AF XY: 0.221 AC XY: 72027 AN XY: 325486

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.199 AC: 30315 AN: 152098 Hom.: 3129 Cov.: 32 AF XY: 0.196 AC XY: 14561 AN XY: 74364

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.214

Alfa AF: 0.212 Hom.: 510

Bravo AF: 0.197

Asia WGS AF: 0.178 AC: 617 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.70
CADD	Benign	0.67
DANN	Benign	0.86

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: rs34742076; hg19: chr8-73942712; COSMIC: COSV52577140; COSMIC: COSV52577140;