rs12334686

Variant names:

• chr8-73024216-G-A
• rs12334686
• NM_017489.3:c.625-606G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.625-606G>A		intron_variant	Intron 4 of 9	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.625-606G>A		intron_variant	Intron 4 of 9	1	NM_017489.3	ENSP00000276603.5

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

African (AFR) AF: 0.117 AC: 4858 AN: 41524

American (AMR) AF: 0.203 AC: 3096 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3470

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5186

South Asian (SAS) AF: 0.222 AC: 1068 AN: 4818

European-Finnish (FIN) AF: 0.389 AC: 4105 AN: 10548

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22563 AN: 67962

Other (OTH) AF: 0.243 AC: 514 AN: 2116

Alfa AF: 0.282 Hom.: 1113

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
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12334686; hg19: chr8-73936451;