8-73027927-A-G

Variant names:

• chr8-73027927-A-G
• rs2981096
• NM_017489.3:c.887+875A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017489.3(TERF1):​c.887+875A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 152,106 control chromosomes in the GnomAD database, including 103 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 0.030 (103 hom., cov: 32)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 3 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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0305 (4638/152106) while in subpopulation NFE AF = 0.0472 (3207/67976). AF 95% confidence interval is 0.0458. There are 103 homozygotes in GnomAd4. There are 2131 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4638 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERF1	NM_017489.3	c.887+875A>G		intron_variant	Intron 6 of 9	ENST00000276603.10	NP_059523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERF1	ENST00000276603.10	c.887+875A>G		intron_variant	Intron 6 of 9	1	NM_017489.3	ENSP00000276603.5

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4639 AN: 151988 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.00833

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00891

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0307

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

GnomAD4 genome AF: 0.0305 AC: 4638 AN: 152106 Hom.: 103 Cov.: 32 AF XY: 0.0287 AC XY: 2131 AN XY: 74350

African (AFR) AF: 0.00831 AC: 345 AN: 41514

American (AMR) AF: 0.0169 AC: 258 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 321 AN: 3460

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00851 AC: 41 AN: 4820

European-Finnish (FIN) AF: 0.0367 AC: 388 AN: 10570

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3207 AN: 67976

Other (OTH) AF: 0.0304 AC: 64 AN: 2104

Alfa AF: 0.0429 Hom.: 108

Bravo AF: 0.0278

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.55
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs2981096; hg19: chr8-73940162;