22-19837476-A-T

Variant names:

• chr22-19837476-A-T
• rs7286924
• NM_053004.3:c.-20-16101T>A

Variant summary

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

The NM_053004.3(GNB1L):​c.-20-16101T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,186 control chromosomes in the GnomAD database, including 3,468 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 0.21 (3468 hom., cov: 33)
• Consequence: GNB1L NM_053004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 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.-20-16101T>A		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.-20-16101T>A		intron	N/A	ENSP00000331313.6
	GNB1L	ENST00000403325.5	TSL:1	c.-20-16101T>A		intron	N/A	ENSP00000385154.1
	GNB1L	ENST00000405009.5	TSL:1	c.-20-16101T>A		intron	N/A	ENSP00000384626.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31714 AN: 152068 Hom.: 3462 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.209 AC: 31743 AN: 152186 Hom.: 3468 Cov.: 33 AF XY: 0.204 AC XY: 15213 AN XY: 74416

African (AFR) AF: 0.188 AC: 7795 AN: 41514

American (AMR) AF: 0.206 AC: 3147 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3466

East Asian (EAS) AF: 0.351 AC: 1818 AN: 5174

South Asian (SAS) AF: 0.168 AC: 813 AN: 4826

European-Finnish (FIN) AF: 0.155 AC: 1642 AN: 10614

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15040 AN: 67982

Other (OTH) AF: 0.216 AC: 456 AN: 2112

Alfa AF: 0.108 Hom.: 162

Bravo AF: 0.217

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.64
PhyloP100		-0.62
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: rs7286924; hg19: chr22-19824999; COSMIC: COSV107345258;