NM_053004.3:c.417+2063C>T

Variant names:

• chr22-19810222-G-A
• rs13057609
• NM_053004.3:c.417+2063C>T

Variant summary

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

The NM_053004.3(GNB1L):​c.417+2063C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 152,236 control chromosomes in the GnomAD database, including 428 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 0.065 (428 hom., cov: 33)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053004.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB1L	NM_053004.3	MANE Select	c.417+2063C>T		intron	N/A	NP_443730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB1L	ENST00000329517.11	TSL:1 MANE Select	c.417+2063C>T		intron	N/A	ENSP00000331313.6
	GNB1L	ENST00000403325.5	TSL:1	c.417+2063C>T		intron	N/A	ENSP00000385154.1
	GNB1L	ENST00000405009.5	TSL:1	c.417+2063C>T		intron	N/A	ENSP00000384626.1

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9974 AN: 152118 Hom.: 428 Cov.: 33

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.0680

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

GnomAD4 genome AF: 0.0655 AC: 9970 AN: 152236 Hom.: 428 Cov.: 33 AF XY: 0.0638 AC XY: 4748 AN XY: 74414

African (AFR) AF: 0.0174 AC: 722 AN: 41554

American (AMR) AF: 0.0592 AC: 905 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3472

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5178

South Asian (SAS) AF: 0.0721 AC: 348 AN: 4826

European-Finnish (FIN) AF: 0.0612 AC: 649 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0979 AC: 6657 AN: 67992

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

Alfa AF: 0.0856 Hom.: 1037

Bravo AF: 0.0636

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13057609; hg19: chr22-19797745;