rs2981096

chr8-73027927-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017489.3(TERF1):c.887+875A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 152,106 control chromosomes in the GnomAD database, including 103 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 0.030 (103 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0305 (4638/152106) while in subpopulation NFE AF= 0.0472 (3207/67976). AF 95% confidence interval is 0.0458. There are 103 homozygotes in gnomad4. There are 2131 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 4639 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERF1	NM_017489.3	c.887+875A>G		intron_variant		ENST00000276603.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERF1	ENST00000276603.10	c.887+875A>G		intron_variant		1	NM_017489.3	P4

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4639 AN: 151988 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.00833

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00891

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0307

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

GnomAD4 genome AF: 0.0305 AC: 4638 AN: 152106 Hom.: 103 Cov.: 32 AF XY: 0.0287 AC XY: 2131 AN XY: 74350

Gnomad4 AFR AF: 0.00831

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0928

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.0458 Hom.: 60

Bravo AF: 0.0278

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.12
Dann	Benign	0.55

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: rs2981096; hg19: chr8-73940162;