chr11-78906144-T-C

Variant names:

• chr11-78906144-T-C
• rs621011
• NM_001098816.3:c.494-2621A>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.494-2621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,208 control chromosomes in the GnomAD database, including 4,724 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 0.24 (4724 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 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.494-2621A>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.494-2621A>G		intron	N/A	ENSP00000278550.7	Q6N022
	TENM4	ENST00000533013.1	TSL:3	n.78-2621A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.243 AC: 37008 AN: 152090 Hom.: 4721 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.243 AC: 37026 AN: 152208 Hom.: 4724 Cov.: 33 AF XY: 0.239 AC XY: 17766 AN XY: 74424

African (AFR) AF: 0.221 AC: 9184 AN: 41522

American (AMR) AF: 0.194 AC: 2964 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 862 AN: 3466

East Asian (EAS) AF: 0.0207 AC: 107 AN: 5180

South Asian (SAS) AF: 0.182 AC: 881 AN: 4828

European-Finnish (FIN) AF: 0.271 AC: 2875 AN: 10592

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19105 AN: 68004

Other (OTH) AF: 0.266 AC: 563 AN: 2116

Alfa AF: 0.259 Hom.: 995

Bravo AF: 0.237

Asia WGS AF: 0.124 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.76
DANN	Benign	0.82
PhyloP100		-0.20
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: rs621011; hg19: chr11-78617189;