chr11-79400778-A-C

Variant names:

• chr11-79400778-A-C
• rs472186
• NM_001098816.3:c.-321+39731T>G

Variant summary

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

The NM_001098816.3(TENM4):​c.-321+39731T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,114 control chromosomes in the GnomAD database, including 33,617 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 0.66 (33617 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 4 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	NM_001098816.3	MANE Select	c.-321+39731T>G		intron	N/A	NP_001092286.2	Q6N022

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM4	ENST00000278550.12	TSL:5 MANE Select	c.-321+39731T>G		intron	N/A	ENSP00000278550.7	Q6N022
	TENM4	ENST00000528688.5	TSL:3	n.239+38184T>G		intron	N/A
	TENM4	ENST00000531583.1	TSL:5	n.440+39731T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100315 AN: 151996 Hom.: 33570 Cov.: 33

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.660 AC: 100429 AN: 152114 Hom.: 33617 Cov.: 33 AF XY: 0.655 AC XY: 48683 AN XY: 74356

African (AFR) AF: 0.785 AC: 32592 AN: 41516

American (AMR) AF: 0.590 AC: 9017 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2061 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3041 AN: 5142

South Asian (SAS) AF: 0.596 AC: 2874 AN: 4826

European-Finnish (FIN) AF: 0.571 AC: 6036 AN: 10572

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42691 AN: 67986

Other (OTH) AF: 0.635 AC: 1344 AN: 2116

Alfa AF: 0.628 Hom.: 20656

Bravo AF: 0.667

Asia WGS AF: 0.614 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.6
DANN	Benign	0.33
PhyloP100		-1.4
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: rs472186; hg19: chr11-79111822;