8-73030477-C-T

Variant names:

• chr8-73030477-C-T
• rs34742076
• NM_017489.3:c.947+82C>T

Variant summary

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

The NM_017489.3(TERF1):​c.947+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 796,956 control chromosomes in the GnomAD database, including 19,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3129 hom., cov: 32)
  • Exomes 𝑓: 0.22 (16709 hom.)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.965
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 8-73030477-C-T is Benign according to our data. Variant chr8-73030477-C-T is described in ClinVar as Benign. ClinVar VariationId is 1268267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 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.947+82C>T		intron	N/A	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.947+82C>T		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.888-1565C>T		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.947+82C>T		intron	N/A	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.888-1565C>T		intron	N/A	ENSP00000276602.6	P54274-2
	TERF1	ENST00000518961.1	TSL:1	n.525C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30301 AN: 151980 Hom.: 3129 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.221 AC: 142452 AN: 644858 Hom.: 16709 Cov.: 9 AF XY: 0.221 AC XY: 72027 AN XY: 325486

African (AFR) AF: 0.155 AC: 2055 AN: 13222

American (AMR) AF: 0.178 AC: 1676 AN: 9412

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 4214 AN: 13218

East Asian (EAS) AF: 0.134 AC: 3260 AN: 24316

South Asian (SAS) AF: 0.201 AC: 6511 AN: 32358

European-Finnish (FIN) AF: 0.169 AC: 7075 AN: 41898

Middle Eastern (MID) AF: 0.254 AC: 569 AN: 2244

European-Non Finnish (NFE) AF: 0.231 AC: 110363 AN: 478150

Other (OTH) AF: 0.224 AC: 6729 AN: 30040

GnomAD4 genome AF: 0.199 AC: 30315 AN: 152098 Hom.: 3129 Cov.: 32 AF XY: 0.196 AC XY: 14561 AN XY: 74364

African (AFR) AF: 0.151 AC: 6271 AN: 41486

American (AMR) AF: 0.177 AC: 2707 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3472

East Asian (EAS) AF: 0.154 AC: 794 AN: 5160

South Asian (SAS) AF: 0.223 AC: 1071 AN: 4800

European-Finnish (FIN) AF: 0.159 AC: 1680 AN: 10592

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15965 AN: 67992

Other (OTH) AF: 0.214 AC: 452 AN: 2110

Alfa AF: 0.210 Hom.: 516

Bravo AF: 0.197

Asia WGS AF: 0.178 AC: 617 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.67
DANN	Benign	0.86
PhyloP100		-0.96
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: rs34742076; hg19: chr8-73942712; COSMIC: COSV52577140; COSMIC: COSV52577140;