22-19783263-C-T

Variant names:

• chr22-19783263-C-T
• rs28605486
• NM_053004.3:c.*5446G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_053004.3(GNB1L):​c.*5446G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00599 in 524,042 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (13 hom.)
• Consequence: GNB1L NM_053004.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.530

Genes affected

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

TBX1 (HGNC:11592): (T-box transcription factor 1) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene product shares 98% amino acid sequence identity with the mouse ortholog. DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), a common congenital disorder characterized by neural-crest-related developmental defects, has been associated with deletions of chromosome 22q11.2, where this gene has been mapped. Studies using mouse models of DiGeorge syndrome suggest a major role for this gene in the molecular etiology of DGS/VCFS. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-19783263-C-T is Benign according to our data. Variant chr22-19783263-C-T is described in ClinVar as [Benign]. Clinvar id is 1277605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3	c.*5446G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000329517.11	NP_443730.1
TBX1	NM_005992.1	c.*11-51C>T		intron_variant	Intron 9 of 9		NP_005983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517	c.*5446G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_053004.3	ENSP00000331313.6
TBX1	ENST00000359500.7	c.*11-51C>T		intron_variant	Intron 9 of 9	1		ENSP00000352483.3

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2398 AN: 152166 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00199 AC: 741 AN: 371760 Hom.: 13 Cov.: 0 AF XY: 0.00167 AC XY: 328 AN XY: 196882

Gnomad4 AFR exome AF: 0.0505 AC: 541 AN: 10716

Gnomad4 AMR exome AF: 0.00371 AC: 63 AN: 17000

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 11344

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 23552

Gnomad4 SAS exome AF: 0.0000665 AC: 3 AN: 45122

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 21448

Gnomad4 NFE exome AF: 0.000182 AC: 40 AN: 219806

Gnomad4 Remaining exome AF: 0.00411 AC: 87 AN: 21192

GnomAD4 genome AF: 0.0157 AC: 2396 AN: 152282 Hom.: 58 Cov.: 32 AF XY: 0.0152 AC XY: 1131 AN XY: 74452

Gnomad4 AFR AF: 0.0545 AC: 0.0545179 AN: 0.0545179

Gnomad4 AMR AF: 0.00582 AC: 0.00581851 AN: 0.00581851

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207039 AN: 0.000207039

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000206 AC: 0.000205816 AN: 0.000205816

Gnomad4 OTH AF: 0.0123 AC: 0.0122873 AN: 0.0122873

Alfa AF: 0.0130 Hom.: 3

Bravo AF: 0.0175

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 09, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.50
Mutation Taster		=100/0	polymorphism

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: rs28605486; hg19: chr22-19770786;