8-73026642-T-A

Variant names:

• chr8-73026642-T-A
• rs55905403
• NM_017489.3:c.775-298T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017489.3(TERF1):​c.775-298T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 152,126 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.016 (60 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.606
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 8-73026642-T-A is Benign according to our data. Variant chr8-73026642-T-A is described in ClinVar as Benign. ClinVar VariationId is 1276310.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 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.775-298T>A		intron	N/A	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.775-298T>A		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.775-298T>A		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.775-298T>A		intron	N/A	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.775-298T>A		intron	N/A	ENSP00000276602.6	P54274-2
	TERF1	ENST00000899325.1		c.775-298T>A		intron	N/A	ENSP00000569384.1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2438 AN: 152008 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000956

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0160 AC: 2436 AN: 152126 Hom.: 60 Cov.: 32 AF XY: 0.0156 AC XY: 1158 AN XY: 74404

African (AFR) AF: 0.0541 AC: 2243 AN: 41468

American (AMR) AF: 0.00667 AC: 102 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000956 AC: 65 AN: 67988

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00274 Hom.: 0

Bravo AF: 0.0182

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.16
PhyloP100		-0.61
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: rs55905403; hg19: chr8-73938877;