rs2975842

Variant names:

• chr8-73013356-T-C
• rs2975842
• NM_017489.3:c.320-539T>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.320-539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,050 control chromosomes in the GnomAD database, including 16,592 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 0.44 (16592 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.320-539T>C		intron_variant	Intron 1 of 9	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.320-539T>C		intron_variant	Intron 1 of 9	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67483 AN: 151932 Hom.: 16596 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.444 AC: 67506 AN: 152050 Hom.: 16592 Cov.: 32 AF XY: 0.440 AC XY: 32733 AN XY: 74316

African (AFR) AF: 0.262 AC: 10863 AN: 41468

American (AMR) AF: 0.379 AC: 5786 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1921 AN: 3464

East Asian (EAS) AF: 0.186 AC: 963 AN: 5178

South Asian (SAS) AF: 0.445 AC: 2146 AN: 4822

European-Finnish (FIN) AF: 0.547 AC: 5773 AN: 10554

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38533 AN: 67978

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.526 Hom.: 87006

Bravo AF: 0.422

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		-0.33
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: rs2975842; hg19: chr8-73925591;