7-93922116-C-T

Variant names:

• chr7-93922116-C-T
• rs4262
• NM_004126.4:c.-22C>T

Variant summary

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

The NM_004126.4(GNG11):​c.-22C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,514,742 control chromosomes in the GnomAD database, including 264,399 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 0.54 (22870 hom., cov: 33)
  • Exomes 𝑓: 0.59 (241529 hom.)
• Consequence: GNG11 NM_004126.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 33 publications found

Genes affected

GNG11 (HGNC:4403): (G protein subunit gamma 11) This gene is a member of the guanine nucleotide-binding protein (G protein) gamma family and encodes a lipid-anchored, cell membrane protein. As a member of the heterotrimeric G protein complex, this protein plays a role in this transmembrane signaling system. This protein is also subject to carboxyl-terminal processing. Decreased expression of this gene is associated with splenic marginal zone lymphomas. [provided by RefSeq, Jul 2008]

ENSG00000306701 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG11	NM_004126.4	c.-22C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000248564.6	NP_004117.1
GNG11	NM_004126.4	c.-22C>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000248564.6	NP_004117.1
LOC105375402	XR_927751.3	n.380-5596G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG11	ENST00000248564.6	c.-22C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_004126.4	ENSP00000248564.4
GNG11	ENST00000248564.6	c.-22C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_004126.4	ENSP00000248564.4
ENSG00000306701	ENST00000820276.1	n.301-9792G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81699 AN: 151982 Hom.: 22872 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.557

GnomAD2 exomes AF: 0.603 AC: 138191 AN: 229150 AF XY: 0.606

Gnomad AFR exome AF: 0.357

Gnomad AMR exome AF: 0.625

Gnomad ASJ exome AF: 0.620

Gnomad EAS exome AF: 0.766

Gnomad FIN exome AF: 0.657

Gnomad NFE exome AF: 0.592

Gnomad OTH exome AF: 0.593

GnomAD4 exome AF: 0.592 AC: 806585 AN: 1362642 Hom.: 241529 Cov.: 20 AF XY: 0.594 AC XY: 401551 AN XY: 676530

African (AFR) AF: 0.354 AC: 11054 AN: 31206

American (AMR) AF: 0.615 AC: 25653 AN: 41692

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 15435 AN: 24526

East Asian (EAS) AF: 0.793 AC: 29909 AN: 37740

South Asian (SAS) AF: 0.614 AC: 48555 AN: 79100

European-Finnish (FIN) AF: 0.654 AC: 33895 AN: 51854

Middle Eastern (MID) AF: 0.578 AC: 3055 AN: 5290

European-Non Finnish (NFE) AF: 0.586 AC: 606761 AN: 1035422

Other (OTH) AF: 0.578 AC: 32268 AN: 55812

GnomAD4 genome AF: 0.537 AC: 81705 AN: 152100 Hom.: 22870 Cov.: 33 AF XY: 0.543 AC XY: 40377 AN XY: 74352

African (AFR) AF: 0.367 AC: 15207 AN: 41490

American (AMR) AF: 0.575 AC: 8791 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2171 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3964 AN: 5154

South Asian (SAS) AF: 0.589 AC: 2845 AN: 4828

European-Finnish (FIN) AF: 0.652 AC: 6905 AN: 10588

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39837 AN: 67966

Other (OTH) AF: 0.553 AC: 1165 AN: 2106

Alfa AF: 0.569 Hom.: 46224

Bravo AF: 0.526

Asia WGS AF: 0.603 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.69
DANN	Benign	0.79
PhyloP100		-1.7
PromoterAI		0.0098	Neutral
Mutation Taster		=300/0	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: rs4262; hg19: chr7-93551428;