rs34368910

Variant names:

• chr8-73046075-T-C
• rs34368910
• NM_017489.3:c.1258T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_017489.3(TERF1):​c.1258T>C​(p.Leu420Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,610,046 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (12 hom.)
• Consequence: TERF1 NM_017489.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.355
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 8-73046075-T-C is Benign according to our data. Variant chr8-73046075-T-C is described in ClinVar as [Benign]. Clinvar id is 784130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.355 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00691 (1052/152302) while in subpopulation AFR AF = 0.0233 (967/41556). AF 95% confidence interval is 0.0221. There are 8 homozygotes in GnomAd4. There are 519 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1052 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.1258T>C	p.Leu420Leu	synonymous_variant	Exon 10 of 10	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.1258T>C	p.Leu420Leu	synonymous_variant	Exon 10 of 10	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes AF: 0.00690 AC: 1050 AN: 152184 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00197 AC: 477 AN: 242158 AF XY: 0.00147

Gnomad AFR exome AF: 0.0245

Gnomad AMR exome AF: 0.00169

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000297

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.000980 AC: 1428 AN: 1457744 Hom.: 12 Cov.: 30 AF XY: 0.000885 AC XY: 642 AN XY: 725140

African (AFR) AF: 0.0282 AC: 937 AN: 33194

American (AMR) AF: 0.00204 AC: 89 AN: 43710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39350

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00488 AC: 28 AN: 5736

European-Non Finnish (NFE) AF: 0.000203 AC: 225 AN: 1110600

Other (OTH) AF: 0.00232 AC: 140 AN: 60226

GnomAD4 genome AF: 0.00691 AC: 1052 AN: 152302 Hom.: 8 Cov.: 32 AF XY: 0.00697 AC XY: 519 AN XY: 74470

African (AFR) AF: 0.0233 AC: 967 AN: 41556

American (AMR) AF: 0.00275 AC: 42 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68028

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00459 Hom.: 1

Bravo AF: 0.00832

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000388

EpiControl AF: 0.000481

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

- -

Jul 10, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs34368910; hg19: chr8-73958310;