rs55915205

Variant names:

• chr8-73027121-G-A
• rs55915205
• NM_017489.3:c.887+69G>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.887+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,088,828 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (28 hom.)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00700
• 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=-0.85).
• BP6: Variant 8-73027121-G-A is Benign according to our data. Variant chr8-73027121-G-A is described in ClinVar as Benign. ClinVar VariationId is 1241756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 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.887+69G>A		intron	N/A	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.887+69G>A		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.887+69G>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.887+69G>A		intron	N/A	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.887+69G>A		intron	N/A	ENSP00000276602.6	P54274-2
	TERF1	ENST00000899325.1		c.887+69G>A		intron	N/A	ENSP00000569384.1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2384 AN: 152090 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00138 AC: 1291 AN: 936618 Hom.: 28 AF XY: 0.00115 AC XY: 550 AN XY: 477666

African (AFR) AF: 0.0517 AC: 1073 AN: 20756

American (AMR) AF: 0.00274 AC: 67 AN: 24444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20070

East Asian (EAS) AF: 0.00 AC: 0 AN: 33056

South Asian (SAS) AF: 0.0000475 AC: 3 AN: 63168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37654

Middle Eastern (MID) AF: 0.000810 AC: 3 AN: 3702

European-Non Finnish (NFE) AF: 0.0000376 AC: 26 AN: 691424

Other (OTH) AF: 0.00281 AC: 119 AN: 42344

GnomAD4 genome AF: 0.0156 AC: 2382 AN: 152210 Hom.: 59 Cov.: 32 AF XY: 0.0151 AC XY: 1122 AN XY: 74424

African (AFR) AF: 0.0547 AC: 2273 AN: 41536

American (AMR) AF: 0.00523 AC: 80 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67992

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.0151 Hom.: 4

Bravo AF: 0.0180

Asia WGS AF: 0.00347 AC: 14 AN: 3470

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	-0.85
CADD	Benign	0.83
DANN	Benign	0.16
PhyloP100		0.0070
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: rs55915205; hg19: chr8-73939356;