chr8-73008928-C-T

Variant names:

• chr8-73008928-C-T
• rs150799660
• NM_017489.3:c.42C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001413365.1(TERF1):​c.-347C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,612,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: TERF1 NM_001413365.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -7.78
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 8-73008928-C-T is Benign according to our data. Variant chr8-73008928-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3034140.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 47 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413365.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	NM_017489.3	MANE Select	c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 10	NP_059523.2	P54274-1
	TERF1	NM_001413365.1		c.-347C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001400294.1
	TERF1	NM_001413366.1		c.-347C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001400295.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	ENST00000276603.10	TSL:1 MANE Select	c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 10	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 9	ENSP00000276602.6	P54274-2
	TERF1	ENST00000899325.1		c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 11	ENSP00000569384.1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000468 AC: 115 AN: 245472 AF XY: 0.000399

Gnomad AFR exome AF: 0.0000649

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000308

Gnomad OTH exome AF: 0.00354

GnomAD4 exome AF: 0.000373 AC: 544 AN: 1460100 Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 263 AN XY: 726200

African (AFR) AF: 0.000239 AC: 8 AN: 33458

American (AMR) AF: 0.00184 AC: 82 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00371 AC: 21 AN: 5658

European-Non Finnish (NFE) AF: 0.000355 AC: 395 AN: 1111428

Other (OTH) AF: 0.000580 AC: 35 AN: 60306

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21 AN XY: 74496

African (AFR) AF: 0.0000962 AC: 4 AN: 41590

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.000263 Hom.: 0

Bravo AF: 0.000438

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TERF1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.32
DANN	Benign	0.90
PhyloP100		-7.8
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism

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: rs150799660; hg19: chr8-73921163;