8-73030122-A-C

Position:

• chr8-73030122-A-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.888-214A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 375,148 control chromosomes in the GnomAD database, including 2,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (816 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1723 hom.)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.168

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=-0.79).
• BP6: Variant 8-73030122-A-C is Benign according to our data. Variant chr8-73030122-A-C is described in ClinVar as [Benign]. Clinvar id is 1233718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF1	NM_017489.3	c.888-214A>C		intron_variant		ENST00000276603.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF1	ENST00000276603.10	c.888-214A>C		intron_variant		1	NM_017489.3	P4

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14193 AN: 152100 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.118 AC: 26252 AN: 222930 Hom.: 1723 Cov.: 0 AF XY: 0.119 AC XY: 13559 AN XY: 113800

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.0908

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.0932 AC: 14186 AN: 152218 Hom.: 816 Cov.: 32 AF XY: 0.0942 AC XY: 7008 AN XY: 74424

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.0930

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.118

Alfa AF: 0.109 Hom.: 439

Bravo AF: 0.0892

Asia WGS AF: 0.151 AC: 524 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 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
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: rs10107605; hg19: chr8-73942357;