rs45617738

Variant names:

• chr2-219253772-TC-T
• rs45617738
• NM_006000.3:c.3+83delG

Your query was ambiguous. Multiple possible variants found:

• chr2-219253772-TC-T
• chr2-219253772-TC-TCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006000.3(TUBA4A):​c.3+83delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,478,208 control chromosomes in the GnomAD database, including 61 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (29 hom.)
• Consequence: TUBA4A NM_006000.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.391
• Publications: 0 publications found

Genes affected

TUBA4A (HGNC:12407): (tubulin alpha 4a) Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulin. The genes encoding these microtubule constituents are part of the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes and they are highly conserved among and between species. This gene encodes an alpha tubulin that is a highly conserved homolog of a rat testis-specific alpha tubulin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

TUBA4B (HGNC:18637): (tubulin alpha 4b) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Predicted to be active in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-219253772-TC-T is Benign according to our data. Variant chr2-219253772-TC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1186396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1595/151506) while in subpopulation AFR AF = 0.0358 (1476/41210). AF 95% confidence interval is 0.0343. There are 32 homozygotes in GnomAd4. There are 751 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1595 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006000.3. 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
	TUBA4A	NM_006000.3	MANE Select	c.3+83delG		intron	N/A	NP_005991.1	P68366-1
	TUBA4B	NM_001355221.1	MANE Select	c.12+357delC		intron	N/A	NP_001342150.1	Q9H853
	TUBA4A	NM_001278552.2		c.-43+322delG		intron	N/A	NP_001265481.1	P68366-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBA4A	ENST00000248437.9	TSL:1 MANE Select	c.3+83delG		intron	N/A	ENSP00000248437.4	P68366-1
	TUBA4B	ENST00000490341.3	TSL:2 MANE Select	c.12+354delC		intron	N/A	ENSP00000487719.1	Q9H853
	TUBA4B	ENST00000473885.5	TSL:1	n.177+354delC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1590 AN: 151390 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00440

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000545

Gnomad OTH AF: 0.00577

GnomAD4 exome AF: 0.00132 AC: 1748 AN: 1326702 Hom.: 29 AF XY: 0.00118 AC XY: 776 AN XY: 656828

African (AFR) AF: 0.0388 AC: 1163 AN: 29942

American (AMR) AF: 0.00277 AC: 83 AN: 29982

Ashkenazi Jewish (ASJ) AF: 0.000604 AC: 14 AN: 23170

East Asian (EAS) AF: 0.00 AC: 0 AN: 34778

South Asian (SAS) AF: 0.0000930 AC: 7 AN: 75246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47920

Middle Eastern (MID) AF: 0.00331 AC: 18 AN: 5446

European-Non Finnish (NFE) AF: 0.000300 AC: 307 AN: 1025004

Other (OTH) AF: 0.00283 AC: 156 AN: 55214

GnomAD4 genome AF: 0.0105 AC: 1595 AN: 151506 Hom.: 32 Cov.: 32 AF XY: 0.0101 AC XY: 751 AN XY: 74014

African (AFR) AF: 0.0358 AC: 1476 AN: 41210

American (AMR) AF: 0.00439 AC: 67 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000545 AC: 37 AN: 67850

Other (OTH) AF: 0.00571 AC: 12 AN: 2102

Alfa AF: 0.00961 Hom.: 5

Bravo AF: 0.0123

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs45617738; hg19: chr2-220118494;