ENST00000518961.1:n.170A>C

Variant names:

• chr8-73030122-A-C
• rs10107605
• ENST00000518961.1:n.170A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000518961.1(TERF1):​n.170A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 375,148 control chromosomes in the GnomAD database, including 2,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (816 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1723 hom.)
• Consequence: TERF1 ENST00000518961.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.168
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-73030122-A-C is Benign according to our data. Variant chr8-73030122-A-C is described in ClinVar as Benign. ClinVar VariationId is 1233718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518961.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	NM_017489.3	MANE Select	c.888-214A>C		intron	N/A	NP_059523.2
	TERF1	NM_001413364.1		c.888-214A>C		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.888-1920A>C		intron	N/A	NP_001397857.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF1	ENST00000518961.1	TSL:1	n.170A>C		non_coding_transcript_exon	Exon 1 of 3
	TERF1	ENST00000276603.10	TSL:1 MANE Select	c.888-214A>C		intron	N/A	ENSP00000276603.5
	TERF1	ENST00000276602.10	TSL:1	c.888-1920A>C		intron	N/A	ENSP00000276602.6

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14193 AN: 152100 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.118 AC: 26252 AN: 222930 Hom.: 1723 Cov.: 0 AF XY: 0.119 AC XY: 13559 AN XY: 113800

African (AFR) AF: 0.0246 AC: 160 AN: 6508

American (AMR) AF: 0.0908 AC: 589 AN: 6484

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 1188 AN: 8134

East Asian (EAS) AF: 0.118 AC: 2342 AN: 19804

South Asian (SAS) AF: 0.109 AC: 427 AN: 3920

European-Finnish (FIN) AF: 0.106 AC: 1987 AN: 18778

Middle Eastern (MID) AF: 0.163 AC: 192 AN: 1176

European-Non Finnish (NFE) AF: 0.123 AC: 17660 AN: 143280

Other (OTH) AF: 0.115 AC: 1707 AN: 14846

GnomAD4 genome AF: 0.0932 AC: 14186 AN: 152218 Hom.: 816 Cov.: 32 AF XY: 0.0942 AC XY: 7008 AN XY: 74424

African (AFR) AF: 0.0225 AC: 935 AN: 41554

American (AMR) AF: 0.0930 AC: 1422 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.111 AC: 572 AN: 5176

South Asian (SAS) AF: 0.125 AC: 601 AN: 4820

European-Finnish (FIN) AF: 0.122 AC: 1286 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8503 AN: 68012

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.112 Hom.: 733

Bravo AF: 0.0892

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.86
PhyloP100		-0.17
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: rs10107605; hg19: chr8-73942357;