chr11-78950453-G-A

Variant names:

• chr11-78950453-G-A
• rs663520
• NM_001098816.3:c.494-46930C>T

Variant summary

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

The NM_001098816.3(TENM4):​c.494-46930C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,012 control chromosomes in the GnomAD database, including 14,596 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 0.43 (14596 hom., cov: 32)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369
• 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: 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.494-46930C>T		intron_variant	Intron 6 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.494-46930C>T		intron_variant	Intron 6 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000529798.1	n.400-25707C>T		intron_variant	Intron 2 of 2	3
TENM4	ENST00000533013.1	n.77+11690C>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65226 AN: 151894 Hom.: 14598 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.429 AC: 65242 AN: 152012 Hom.: 14596 Cov.: 32 AF XY: 0.423 AC XY: 31394 AN XY: 74274

African (AFR) AF: 0.471 AC: 19528 AN: 41460

American (AMR) AF: 0.354 AC: 5405 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1673 AN: 3464

East Asian (EAS) AF: 0.0564 AC: 291 AN: 5162

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4814

European-Finnish (FIN) AF: 0.391 AC: 4134 AN: 10560

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31198 AN: 67976

Other (OTH) AF: 0.436 AC: 921 AN: 2110

Alfa AF: 0.436 Hom.: 2960

Bravo AF: 0.427

Asia WGS AF: 0.183 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.72
PhyloP100		0.37
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: rs663520; hg19: chr11-78661498;