chr8-73014630-G-C

Variant names:

• chr8-73014630-G-C
• rs2929585
• NM_017489.3:c.415+640G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017489.3(TERF1):​c.415+640G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 151,884 control chromosomes in the GnomAD database, including 35,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35545 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.415+640G>C		intron_variant	Intron 2 of 9	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.415+640G>C		intron_variant	Intron 2 of 9	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102752 AN: 151766 Hom.: 35518 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.686

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.677 AC: 102837 AN: 151884 Hom.: 35545 Cov.: 32 AF XY: 0.671 AC XY: 49786 AN XY: 74216

African (AFR) AF: 0.744 AC: 30840 AN: 41476

American (AMR) AF: 0.528 AC: 8065 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2419 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1661 AN: 5166

South Asian (SAS) AF: 0.591 AC: 2849 AN: 4818

European-Finnish (FIN) AF: 0.695 AC: 7318 AN: 10524

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47527 AN: 67850

Other (OTH) AF: 0.689 AC: 1452 AN: 2108

Alfa AF: 0.689 Hom.: 4554

Bravo AF: 0.666

Asia WGS AF: 0.516 AC: 1795 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.88
PhyloP100		-1.4
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: rs2929585; hg19: chr8-73926865;