4-181949210-C-T

Variant names:

• chr4-181949210-C-T
• rs6852460
• XM_017008385.2:c.-156+81378C>T

Variant summary

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

The ENST00000509012.5(TENM3-AS1):​n.378+63452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,990 control chromosomes in the GnomAD database, including 24,871 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 0.57 (24871 hom., cov: 33)
• Consequence: TENM3-AS1 ENST00000509012.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 1 publications found

Genes affected

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

ENSG00000299420 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509012.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENM3-AS1	ENST00000509012.5	TSL:4	n.378+63452G>A		intron	N/A
	ENSG00000299420	ENST00000763322.1		n.245+81378C>T		intron	N/A
	ENSG00000299420	ENST00000763323.1		n.245+81378C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85894 AN: 151872 Hom.: 24842 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.566 AC: 85971 AN: 151990 Hom.: 24871 Cov.: 33 AF XY: 0.563 AC XY: 41821 AN XY: 74276

African (AFR) AF: 0.652 AC: 27015 AN: 41464

American (AMR) AF: 0.430 AC: 6574 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2109 AN: 5142

South Asian (SAS) AF: 0.614 AC: 2960 AN: 4820

European-Finnish (FIN) AF: 0.543 AC: 5732 AN: 10554

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38118 AN: 67960

Other (OTH) AF: 0.558 AC: 1175 AN: 2104

Alfa AF: 0.492 Hom.: 2781

Bravo AF: 0.558

Asia WGS AF: 0.525 AC: 1827 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.2
DANN	Benign	0.51
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs6852460; hg19: chr4-182870363;