rs1053395

Variant names:

• chr19-6494360-G-C
• rs1053395
• NM_006087.4:c.*804C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-6494360-G-C
• chr19-6494360-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006087.4(TUBB4A):​c.*804C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,798 control chromosomes in the GnomAD database, including 4,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4207 hom., cov: 31)
  • Exomes 𝑓: 0.20 (2 hom.)
• Consequence: TUBB4A NM_006087.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.27

Genes affected

TUBB4A (HGNC:20774): (tubulin beta 4A class IVa) This gene encodes a member of the beta tubulin family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene cause hypomyelinating leukodystrophy-6 and autosomal dominant torsion dystonia-4. Alternate splicing results in multiple transcript variants encoding different isoforms. A pseudogene of this gene is found on chromosome X. [provided by RefSeq, Jan 2014]

ENSG00000268191 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-6494360-G-C is Benign according to our data. Variant chr19-6494360-G-C is described in ClinVar as [Benign]. Clinvar id is 330247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBB4A	NM_006087.4	c.*804C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000264071.7	NP_006078.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBB4A	ENST00000264071	c.*804C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_006087.4	ENSP00000264071.1
ENSG00000268191	ENST00000596027.1	n.41G>C		non_coding_transcript_exon_variant	Exon 1 of 2	5
ENSG00000268203	ENST00000599292.1	n.41G>C		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32978 AN: 151588 Hom.: 4202 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.205 AC: 18 AN: 88 Hom.: 2 Cov.: 0 AF XY: 0.232 AC XY: 13 AN XY: 56

Gnomad4 AFR exome AF: 0.250

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.217 AC: 32994 AN: 151710 Hom.: 4207 Cov.: 31 AF XY: 0.226 AC XY: 16783 AN XY: 74146

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.220

Alfa AF: 0.131 Hom.: 258

Bravo AF: 0.218

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Torsion dystonia 4 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Hypomyelinating leukodystrophy 6 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.41

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: rs1053395; hg19: chr19-6494371;