rs1369458

Positions:

• chr11-79049428-T-C

Variant summary

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

The NM_001098816.3(TENM4):​c.493+15310A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,198 control chromosomes in the GnomAD database, including 1,466 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 0.13 (1466 hom., cov: 34)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM4	NM_001098816.3	c.493+15310A>G		intron_variant		ENST00000278550.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM4	ENST00000278550.12	c.493+15310A>G		intron_variant		5	NM_001098816.3	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20082 AN: 152080 Hom.: 1466 Cov.: 34

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.132 AC: 20098 AN: 152198 Hom.: 1466 Cov.: 34 AF XY: 0.130 AC XY: 9692 AN XY: 74408

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.0995

Gnomad4 SAS AF: 0.0669

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.140

Alfa AF: 0.115 Hom.: 1461

Bravo AF: 0.136

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.59

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: rs1369458; hg19: chr11-78760473;