8-73021004-T-C

Position:

• chr8-73021004-T-C

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.537+199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,886 control chromosomes in the GnomAD database, including 27,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.59 (27852 hom., cov: 31)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.63

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]

TERF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 8-73021004-T-C is Benign according to our data. Variant chr8-73021004-T-C is described in ClinVar as [Benign]. Clinvar id is 1241338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TERF1	NM_017489.3	c.537+199T>C		intron_variant		ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.537+199T>C		intron_variant		1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90274 AN: 151768 Hom.: 27861 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.595 AC: 90303 AN: 151886 Hom.: 27852 Cov.: 31 AF XY: 0.590 AC XY: 43787 AN XY: 74202

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.621

Alfa AF: 0.619 Hom.: 7329

Bravo AF: 0.576

Asia WGS AF: 0.470 AC: 1634 AN: 3474

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	-0.98
CADD	Benign	0.52
DANN	Benign	0.54

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: rs2975853; hg19: chr8-73933239;