4-181859415-G-A

Variant names:

• chr4-181859415-G-A
• rs1914369
• ENST00000715797.1:n.187+15020C>T

Variant summary

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

The ENST00000715797.1(TENM3-AS1):​n.187+15020C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 151,948 control chromosomes in the GnomAD database, including 46,271 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 (46271 hom., cov: 30)
• Consequence: TENM3-AS1 ENST00000715797.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 2 publications found

Genes affected

TENM3-AS1 (HGNC:28076): (TENM3 antisense RNA 1)

ENSG00000299420 (HGNC:):

TENM3 (HGNC:29944): (teneurin transmembrane protein 3) This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

TENM3 Gene-Disease associations (from GenCC):

• microphthalmia, isolated, with coloboma 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• microphthalmia, isolated, with coloboma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000715797.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3-AS1	ENST00000715797.1		n.187+15020C>T		intron	N/A
	ENSG00000299420	ENST00000763321.1		n.568-8337G>A		intron	N/A
	ENSG00000299420	ENST00000763322.1		n.165-8337G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118080 AN: 151830 Hom.: 46229 Cov.: 30

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.778 AC: 118179 AN: 151948 Hom.: 46271 Cov.: 30 AF XY: 0.780 AC XY: 57892 AN XY: 74240

African (AFR) AF: 0.826 AC: 34212 AN: 41428

American (AMR) AF: 0.795 AC: 12141 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2912 AN: 3468

East Asian (EAS) AF: 0.950 AC: 4915 AN: 5176

South Asian (SAS) AF: 0.820 AC: 3939 AN: 4802

European-Finnish (FIN) AF: 0.764 AC: 8056 AN: 10548

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49702 AN: 67946

Other (OTH) AF: 0.772 AC: 1628 AN: 2110

Alfa AF: 0.751 Hom.: 166599

Bravo AF: 0.781

Asia WGS AF: 0.891 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.46
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1914369; hg19: chr4-182780568;