rs489758

Positions:

• chr11-78821746-C-T

Variant summary

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

The NM_001098816.3(TENM4):​c.1682-7351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,018 control chromosomes in the GnomAD database, including 15,019 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 0.44 (15019 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM4	NM_001098816.3	c.1682-7351G>A		intron_variant		ENST00000278550.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM4	ENST00000278550.12	c.1682-7351G>A		intron_variant		5	NM_001098816.3	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66077 AN: 151898 Hom.: 15002 Cov.: 33

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.435 AC: 66129 AN: 152018 Hom.: 15019 Cov.: 33 AF XY: 0.433 AC XY: 32176 AN XY: 74312

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.449

Alfa AF: 0.426 Hom.: 7128

Bravo AF: 0.421

Asia WGS AF: 0.251 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.92

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: rs489758; hg19: chr11-78532791;