rs472186

Positions:

• chr11-79400778-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM4	NM_001098816.3	c.-321+39731T>G		intron_variant		ENST00000278550.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM4	ENST00000278550.12	c.-321+39731T>G		intron_variant		5	NM_001098816.3	P1
TENM4	ENST00000528688.5	n.239+38184T>G		intron_variant, non_coding_transcript_variant		3
TENM4	ENST00000531583.1	n.440+39731T>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.635

Alfa AF: 0.630 Hom.: 15542

Bravo AF: 0.667

Asia WGS AF: 0.614 AC: 2136 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	1.6
DANN	Benign	0.33

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: rs472186; hg19: chr11-79111822;