rs528048

Variant names:

• chr11-79353581-C-T
• rs528048
• NM_001098816.3:c.-320-56038G>A

Variant summary

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

The NM_001098816.3(TENM4):​c.-320-56038G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,082 control chromosomes in the GnomAD database, including 47,057 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 0.78 (47057 hom., cov: 31)
• Consequence: TENM4 NM_001098816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 1 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM4	NM_001098816.3	c.-320-56038G>A		intron_variant	Intron 1 of 33	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12	c.-320-56038G>A		intron_variant	Intron 1 of 33	5	NM_001098816.3	ENSP00000278550.7
TENM4	ENST00000528688.5	n.240-56038G>A		intron_variant	Intron 1 of 3	3
TENM4	ENST00000531583.1	n.441-56038G>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119065 AN: 151964 Hom.: 47000 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.784 AC: 119183 AN: 152082 Hom.: 47057 Cov.: 31 AF XY: 0.782 AC XY: 58092 AN XY: 74322

African (AFR) AF: 0.858 AC: 35609 AN: 41506

American (AMR) AF: 0.713 AC: 10902 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2669 AN: 3466

East Asian (EAS) AF: 0.597 AC: 3067 AN: 5140

South Asian (SAS) AF: 0.677 AC: 3260 AN: 4816

European-Finnish (FIN) AF: 0.813 AC: 8598 AN: 10570

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.773 AC: 52520 AN: 67984

Other (OTH) AF: 0.764 AC: 1614 AN: 2112

Alfa AF: 0.779 Hom.: 6177

Bravo AF: 0.783

Asia WGS AF: 0.675 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.038
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: rs528048; hg19: chr11-79064626;