rs11826937

Variant names:

• chr11-78948100-A-T
• rs11826937
• NM_001098816.3:c.494-44577T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098816.3(TENM4):​c.494-44577T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0899 in 152,196 control chromosomes in the GnomAD database, including 1,073 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 0.090 (1073 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• tremor, hereditary essential, 5

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098816.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	NM_001098816.3	MANE Select	c.494-44577T>A		intron	N/A	NP_001092286.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	ENST00000278550.12	TSL:5 MANE Select	c.494-44577T>A		intron	N/A	ENSP00000278550.7
	TENM4	ENST00000529798.1	TSL:3	n.400-23354T>A		intron	N/A
	TENM4	ENST00000533013.1	TSL:3	n.77+14043T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13640 AN: 152078 Hom.: 1069 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0946

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

GnomAD4 genome AF: 0.0899 AC: 13687 AN: 152196 Hom.: 1073 Cov.: 33 AF XY: 0.0906 AC XY: 6743 AN XY: 74418

African (AFR) AF: 0.195 AC: 8112 AN: 41494

American (AMR) AF: 0.0718 AC: 1098 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1190 AN: 5170

South Asian (SAS) AF: 0.126 AC: 606 AN: 4820

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2048 AN: 68014

Other (OTH) AF: 0.0988 AC: 209 AN: 2116

Alfa AF: 0.0569 Hom.: 68

Bravo AF: 0.0969

Asia WGS AF: 0.197 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.011
DANN	Benign	0.40
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs11826937; hg19: chr11-78659145;