rs504578

Positions:

• chr11-79151247-G-A
• chr11-79151247-G-C

Variant summary

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

The NM_001098816.3(TENM4):​c.-162-2441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,262 control chromosomes in the GnomAD database, including 65,440 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 0.92 (65440 hom., cov: 33)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM4	NM_001098816.3	c.-162-2441C>T		intron_variant		ENST00000278550.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM4	ENST00000278550.12	c.-162-2441C>T		intron_variant		5	NM_001098816.3	P1

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140355 AN: 152144 Hom.: 65390 Cov.: 33

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.923 AC: 140463 AN: 152262 Hom.: 65440 Cov.: 33 AF XY: 0.914 AC XY: 68010 AN XY: 74446

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.980

Gnomad4 OTH AF: 0.937

Alfa AF: 0.945 Hom.: 9054

Bravo AF: 0.916

Asia WGS AF: 0.731 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
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: rs504578; hg19: chr11-78862292;