rs2306494

Variant names:

• chr8-73038992-G-A
• rs2306494
• NM_017489.3:c.1040-124G>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.1040-124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 831,048 control chromosomes in the GnomAD database, including 178,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27861 hom., cov: 32)
  • Exomes 𝑓: 0.66 (151062 hom.)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.349
• Publications: 5 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=-0.93).
• BP6: Variant 8-73038992-G-A is Benign according to our data. Variant chr8-73038992-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294451.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 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.1040-124G>A		intron	N/A	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.1130-124G>A		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.1070-124G>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.1040-124G>A		intron	N/A	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.980-124G>A		intron	N/A	ENSP00000276602.6	P54274-2
	TERF1	ENST00000518961.1	TSL:1	n.2182-124G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90327 AN: 151842 Hom.: 27870 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.658 AC: 447082 AN: 679088 Hom.: 151062 AF XY: 0.656 AC XY: 226758 AN XY: 345668

African (AFR) AF: 0.487 AC: 7578 AN: 15550

American (AMR) AF: 0.479 AC: 7373 AN: 15400

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 10297 AN: 14430

East Asian (EAS) AF: 0.275 AC: 8325 AN: 30252

South Asian (SAS) AF: 0.593 AC: 23781 AN: 40090

European-Finnish (FIN) AF: 0.662 AC: 26805 AN: 40514

Middle Eastern (MID) AF: 0.726 AC: 1697 AN: 2336

European-Non Finnish (NFE) AF: 0.698 AC: 340517 AN: 488096

Other (OTH) AF: 0.639 AC: 20709 AN: 32420

GnomAD4 genome AF: 0.595 AC: 90356 AN: 151960 Hom.: 27861 Cov.: 32 AF XY: 0.591 AC XY: 43864 AN XY: 74278

African (AFR) AF: 0.478 AC: 19793 AN: 41418

American (AMR) AF: 0.498 AC: 7597 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2410 AN: 3468

East Asian (EAS) AF: 0.300 AC: 1550 AN: 5168

South Asian (SAS) AF: 0.582 AC: 2804 AN: 4820

European-Finnish (FIN) AF: 0.671 AC: 7082 AN: 10556

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47107 AN: 67948

Other (OTH) AF: 0.620 AC: 1310 AN: 2112

Alfa AF: 0.652 Hom.: 14417

Bravo AF: 0.575

Asia WGS AF: 0.470 AC: 1626 AN: 3458

ClinVar

ClinVar submissions

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	-0.93
CADD	Benign	2.9
DANN	Benign	0.37
PhyloP100		0.35
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2306494;

hg19: chr8-73951227;