chr8-73045305-C-T

Variant names:

• chr8-73045305-C-T
• rs1545827
• NM_017489.3:c.1144-656C>T

Variant summary

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

The NM_017489.3(TERF1):​c.1144-656C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,956 control chromosomes in the GnomAD database, including 11,568 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 0.37 (11568 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017489.3. 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.1144-656C>T		intron	N/A	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.1234-656C>T		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.1174-656C>T		intron	N/A	NP_001397857.1	A0A7I2YQE7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	ENST00000276603.10	TSL:1 MANE Select	c.1144-656C>T		intron	N/A	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.1084-656C>T		intron	N/A	ENSP00000276602.6	P54274-2
	TERF1	ENST00000518961.1	TSL:1	n.2286-656C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56891 AN: 151838 Hom.: 11573 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.374 AC: 56905 AN: 151956 Hom.: 11568 Cov.: 32 AF XY: 0.374 AC XY: 27788 AN XY: 74272

African (AFR) AF: 0.256 AC: 10590 AN: 41412

American (AMR) AF: 0.313 AC: 4779 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3468

East Asian (EAS) AF: 0.144 AC: 747 AN: 5172

South Asian (SAS) AF: 0.359 AC: 1728 AN: 4820

European-Finnish (FIN) AF: 0.513 AC: 5406 AN: 10544

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31099 AN: 67952

Other (OTH) AF: 0.388 AC: 821 AN: 2114

Alfa AF: 0.426 Hom.: 18307

Bravo AF: 0.354

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.69
PhyloP100		-1.0
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: rs1545827; hg19: chr8-73957540;