rs2234321

Variant names:

• chr22-18110514-G-A
• rs2234321
• ENST00000474897.6:n.815-10965G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-18110514-G-A
• chr22-18110514-G-C
• chr22-18110514-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000474897.6(ENSG00000288683):​n.815-10965G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00731 in 422,164 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (72 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (11 hom.)
• Consequence: ENSG00000288683 ENST00000474897.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.691
• Publications: 0 publications found

Genes affected

ENSG00000288683 (HGNC:):

TUBA8 (HGNC:12410): (tubulin alpha 8) This gene encodes a member of the alpha tubulin protein family. Alpha tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. Mutations in this gene are associated with polymicrogyria and optic nerve hypoplasia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

TUBA8 Gene-Disease associations (from GenCC):

• polymicrogyria with optic nerve hypoplasia

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-18110514-G-A is Benign according to our data. Variant chr22-18110514-G-A is described in ClinVar as Benign. ClinVar VariationId is 1246318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474897.6. 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
	ENSG00000288683	ENST00000474897.6	TSL:5	n.815-10965G>A		intron	N/A	ENSP00000434235.2	E9PRC5
	TUBA8	ENST00000901606.1		c.-352G>A		5_prime_UTR	Exon 1 of 5	ENSP00000571665.1
	TUBA8	ENST00000901605.1		c.-352G>A		5_prime_UTR	Exon 1 of 5	ENSP00000571664.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2558 AN: 152222 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.0581

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.00192 AC: 518 AN: 269824 Hom.: 11 Cov.: 0 AF XY: 0.00180 AC XY: 254 AN XY: 141436

African (AFR) AF: 0.0569 AC: 323 AN: 5672

American (AMR) AF: 0.00523 AC: 33 AN: 6304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8680

East Asian (EAS) AF: 0.00 AC: 0 AN: 16914

South Asian (SAS) AF: 0.000374 AC: 9 AN: 24070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20294

Middle Eastern (MID) AF: 0.00153 AC: 2 AN: 1308

European-Non Finnish (NFE) AF: 0.000429 AC: 73 AN: 169994

Other (OTH) AF: 0.00470 AC: 78 AN: 16588

GnomAD4 genome AF: 0.0169 AC: 2568 AN: 152340 Hom.: 72 Cov.: 32 AF XY: 0.0161 AC XY: 1199 AN XY: 74488

African (AFR) AF: 0.0582 AC: 2419 AN: 41576

American (AMR) AF: 0.00679 AC: 104 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68032

Other (OTH) AF: 0.00995 AC: 21 AN: 2110

Alfa AF: 0.00935 Hom.: 5

Bravo AF: 0.0187

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.77
PhyloP100		-0.69
PromoterAI		0.0055	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2234321; hg19: chr22-18593280;