NM_017489.3:c.947+82C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017489.3(TERF1):​c.947+82C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000433 in 646,312 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: TERF1 NM_017489.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.965
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

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>A		intron	N/A	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.947+82C>A		intron	N/A	NP_001400293.1
	TERF1	NM_001410928.1		c.888-1565C>A		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>A		intron	N/A	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.888-1565C>A		intron	N/A	ENSP00000276602.6	P54274-2
	TERF1	ENST00000518961.1	TSL:1	n.525C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000433 AC: 28 AN: 646312 Hom.: 0 Cov.: 9 AF XY: 0.0000521 AC XY: 17 AN XY: 326188

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000755 AC: 1 AN: 13240

American (AMR) AF: 0.000319 AC: 3 AN: 9414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13236

East Asian (EAS) AF: 0.000123 AC: 3 AN: 24320

South Asian (SAS) AF: 0.00 AC: 0 AN: 32444

European-Finnish (FIN) AF: 0.0000238 AC: 1 AN: 41942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2250

European-Non Finnish (NFE) AF: 0.0000375 AC: 18 AN: 479382

Other (OTH) AF: 0.0000665 AC: 2 AN: 30084

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.53
DANN	Benign	0.84
PhyloP100		-0.96

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;