NM_005652.5:c.*220A>G

Variant names:

• chr16-69356678-T-C
• rs56106543
• NM_005652.5:c.*220A>G

Variant summary

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

The NM_005652.5(TERF2):​c.*220A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 438,718 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (141 hom., cov: 32)
  • Exomes 𝑓: 0.049 (401 hom.)
• Consequence: TERF2 NM_005652.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.147
• Publications: 4 publications found

Genes affected

TERF2 (HGNC:11729): (telomeric repeat binding factor 2) This gene encodes a telomere specific protein, TERF2, which is a component of the telomere nucleoprotein complex. This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length and plays a key role in the protective activity of telomeres. While having similar telomere binding activity and domain organization, TERF2 differs from TERF1 in that its N terminus is basic rather than acidic. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-69356678-T-C is Benign according to our data. Variant chr16-69356678-T-C is described in ClinVar as Benign. ClinVar VariationId is 1228096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005652.5. 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
	TERF2	NM_005652.5	MANE Select	c.*220A>G		3_prime_UTR	Exon 10 of 10	NP_005643.2	Q15554-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TERF2	ENST00000254942.8	TSL:1 MANE Select	c.*220A>G		3_prime_UTR	Exon 10 of 10	ENSP00000254942.3	Q15554-3
	TERF2	ENST00000903039.1		c.*220A>G		3_prime_UTR	Exon 10 of 10	ENSP00000573098.1
	TERF2	ENST00000966429.1		c.*220A>G		3_prime_UTR	Exon 10 of 10	ENSP00000636488.1

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5539 AN: 151684 Hom.: 141 Cov.: 32

Gnomad AFR AF: 0.00930

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0334

GnomAD4 exome AF: 0.0488 AC: 14005 AN: 286920 Hom.: 401 Cov.: 5 AF XY: 0.0499 AC XY: 7520 AN XY: 150652

African (AFR) AF: 0.0120 AC: 94 AN: 7838

American (AMR) AF: 0.0173 AC: 159 AN: 9210

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 500 AN: 8796

East Asian (EAS) AF: 0.00 AC: 0 AN: 19312

South Asian (SAS) AF: 0.0614 AC: 1535 AN: 25000

European-Finnish (FIN) AF: 0.0431 AC: 753 AN: 17470

Middle Eastern (MID) AF: 0.0327 AC: 40 AN: 1222

European-Non Finnish (NFE) AF: 0.0562 AC: 10203 AN: 181546

Other (OTH) AF: 0.0436 AC: 721 AN: 16526

GnomAD4 genome AF: 0.0365 AC: 5537 AN: 151798 Hom.: 141 Cov.: 32 AF XY: 0.0363 AC XY: 2692 AN XY: 74140

African (AFR) AF: 0.00928 AC: 384 AN: 41396

American (AMR) AF: 0.0203 AC: 309 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3468

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5144

South Asian (SAS) AF: 0.0549 AC: 264 AN: 4810

European-Finnish (FIN) AF: 0.0450 AC: 471 AN: 10478

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0559 AC: 3798 AN: 67936

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.0465 Hom.: 24

Bravo AF: 0.0336

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	6.4
DANN	Benign	0.53
PhyloP100		0.15
PromoterAI		0.013	Neutral
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: rs56106543; hg19: chr16-69390581;