rs681267

Positions:

• chr11-78967637-G-A
• chr11-78967637-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098816.3(TENM4):​c.494-64114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,110 control chromosomes in the GnomAD database, including 7,452 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 0.30 (7452 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

Genes affected

TENM4 (HGNC:29945): (teneurin transmembrane protein 4) The protein encoded by this gene plays a role in establishing proper neuronal connectivity during development. Defects in this gene have been associated with hereditary essential tremor-5. [provided by RefSeq, Oct 2016]

TENM4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.494-64114C>T		intron_variant		ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.494-64114C>T		intron_variant		5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000529798.1	n.400-42891C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44890 AN: 151992 Hom.: 7457 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.295 AC: 44889 AN: 152110 Hom.: 7452 Cov.: 32 AF XY: 0.289 AC XY: 21524 AN XY: 74354

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.321

Alfa AF: 0.250 Hom.: 864

Bravo AF: 0.288

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs681267; hg19: chr11-78678682;