8-73020195-T-C

Variant names:

• chr8-73020195-T-C
• rs2975852
• NM_017489.3:c.416-489T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017489.3(TERF1):​c.416-489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,072 control chromosomes in the GnomAD database, including 26,334 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 0.57 (26334 hom., cov: 33)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.416-489T>C		intron_variant	Intron 2 of 9	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.416-489T>C		intron_variant	Intron 2 of 9	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86836 AN: 151952 Hom.: 26340 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.571 AC: 86868 AN: 152072 Hom.: 26334 Cov.: 33 AF XY: 0.567 AC XY: 42164 AN XY: 74338

African (AFR) AF: 0.399 AC: 16542 AN: 41494

American (AMR) AF: 0.490 AC: 7481 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2414 AN: 3472

East Asian (EAS) AF: 0.297 AC: 1537 AN: 5170

South Asian (SAS) AF: 0.576 AC: 2779 AN: 4826

European-Finnish (FIN) AF: 0.670 AC: 7082 AN: 10564

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47066 AN: 67948

Other (OTH) AF: 0.601 AC: 1268 AN: 2110

Alfa AF: 0.634 Hom.: 53370

Bravo AF: 0.549

Asia WGS AF: 0.456 AC: 1585 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.64
PhyloP100		-2.9
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: rs2975852; hg19: chr8-73932430;