chr8-73024941-A-G

Variant names:

• chr8-73024941-A-G
• rs144319719
• NM_017489.3:c.744A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_017489.3(TERF1):​c.744A>G​(p.Leu248Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,577,418 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: TERF1 NM_017489.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.00800
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-73024941-A-G is Benign according to our data. Variant chr8-73024941-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3043905.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.008 with no splicing effect.
• BS2: High AC in GnomAd4 at 66 AD gene.

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.744A>G	p.Leu248Leu	synonymous	Exon 5 of 10	NP_059523.2	P54274-1
	TERF1	NM_001413364.1		c.744A>G	p.Leu248Leu	synonymous	Exon 5 of 11	NP_001400293.1
	TERF1	NM_001410928.1		c.744A>G	p.Leu248Leu	synonymous	Exon 5 of 10	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.744A>G	p.Leu248Leu	synonymous	Exon 5 of 10	ENSP00000276603.5	P54274-1
	TERF1	ENST00000276602.10	TSL:1	c.744A>G	p.Leu248Leu	synonymous	Exon 5 of 9	ENSP00000276602.6	P54274-2
	TERF1	ENST00000899325.1		c.744A>G	p.Leu248Leu	synonymous	Exon 5 of 11	ENSP00000569384.1

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000428 AC: 98 AN: 229210 AF XY: 0.000543

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000329

Gnomad ASJ exome AF: 0.00345

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000390

Gnomad OTH exome AF: 0.00104

GnomAD4 exome AF: 0.000252 AC: 359 AN: 1425058 Hom.: 1 Cov.: 27 AF XY: 0.000277 AC XY: 197 AN XY: 710366

African (AFR) AF: 0.000184 AC: 6 AN: 32668

American (AMR) AF: 0.000537 AC: 22 AN: 40934

Ashkenazi Jewish (ASJ) AF: 0.00379 AC: 98 AN: 25846

East Asian (EAS) AF: 0.00 AC: 0 AN: 39216

South Asian (SAS) AF: 0.000180 AC: 15 AN: 83198

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40444

Middle Eastern (MID) AF: 0.00342 AC: 19 AN: 5550

European-Non Finnish (NFE) AF: 0.000139 AC: 153 AN: 1097762

Other (OTH) AF: 0.000757 AC: 45 AN: 59440

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152360 Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22 AN XY: 74512

African (AFR) AF: 0.0000721 AC: 3 AN: 41590

American (AMR) AF: 0.00229 AC: 35 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000475 Hom.: 0

Bravo AF: 0.000786

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TERF1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		0.0080
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs144319719; hg19: chr8-73937176;