rs12334686

chr8-73024216-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017489.3(TERF1):c.625-606G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,116 control chromosomes in the GnomAD database, including 5,563 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 0.25 (5563 hom., cov: 33)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF1	NM_017489.3	c.625-606G>A		intron_variant		ENST00000276603.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF1	ENST00000276603.10	c.625-606G>A		intron_variant		1	NM_017489.3	P4

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37476 AN: 151998 Hom.: 5568 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.246 AC: 37486 AN: 152116 Hom.: 5563 Cov.: 33 AF XY: 0.246 AC XY: 18312 AN XY: 74338

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.243

Alfa AF: 0.286 Hom.: 1100

Bravo AF: 0.226

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.4
Dann	Benign	0.78

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: rs12334686; hg19: chr8-73936451;