8-73026900-A-G

Variant names:

• chr8-73026900-A-G
• rs16938556
• NM_017489.3:c.775-40A>G

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.775-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,483,748 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.016 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (43 hom.)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.391
• 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-73026900-A-G is Benign according to our data. Variant chr8-73026900-A-G is described in ClinVar as Benign. ClinVar VariationId is 1294460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 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.775-40A>G		intron	N/A	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.775-40A>G		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.775-40A>G		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.775-40A>G		intron	N/A	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.775-40A>G		intron	N/A	ENSP00000276602.6	P54274-2
	TERF1	ENST00000899325.1		c.775-40A>G		intron	N/A	ENSP00000569384.1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2386 AN: 152178 Hom.: 60 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

GnomAD2 exomes AF: 0.00394 AC: 927 AN: 235558 AF XY: 0.00292

Gnomad AFR exome AF: 0.0551

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000103

Gnomad OTH exome AF: 0.000854

GnomAD4 exome AF: 0.00145 AC: 1937 AN: 1331452 Hom.: 43 Cov.: 19 AF XY: 0.00123 AC XY: 820 AN XY: 669152

African (AFR) AF: 0.0543 AC: 1649 AN: 30342

American (AMR) AF: 0.00241 AC: 100 AN: 41508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25078

East Asian (EAS) AF: 0.00 AC: 0 AN: 38914

South Asian (SAS) AF: 0.0000368 AC: 3 AN: 81580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52726

Middle Eastern (MID) AF: 0.00103 AC: 4 AN: 3872

European-Non Finnish (NFE) AF: 0.0000270 AC: 27 AN: 1001482

Other (OTH) AF: 0.00275 AC: 154 AN: 55950

GnomAD4 genome AF: 0.0157 AC: 2384 AN: 152296 Hom.: 60 Cov.: 32 AF XY: 0.0151 AC XY: 1126 AN XY: 74470

African (AFR) AF: 0.0547 AC: 2275 AN: 41566

American (AMR) AF: 0.00523 AC: 80 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.00564 Hom.: 21

Bravo AF: 0.0180

Asia WGS AF: 0.00346 AC: 14 AN: 3478

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	-0.82
CADD	Benign	3.7
DANN	Benign	0.63
PhyloP100		-0.39
BranchPoint Hunter		0.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16938556; hg19: chr8-73939135;