rs8092

Positions:

• chr19-3123637-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002067.5(GNA11):​c.*2458C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 232,848 control chromosomes in the GnomAD database, including 11,571 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 0.31 (7495 hom., cov: 33)
  • Exomes 𝑓: 0.31 (4076 hom.)
• Consequence: GNA11 NM_002067.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

Genes affected

GNA11 (HGNC:4379): (G protein subunit alpha 11) The protein encoded by this gene belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes one of the alpha subunits (subunit alpha-11). Mutations in this gene have been associated with hypocalciuric hypercalcemia type II (HHC2) and hypocalcemia dominant 2 (HYPOC2). Patients with HHC2 and HYPOC2 exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA11	NM_002067.5	c.*2458C>T		3_prime_UTR_variant	7/7	ENST00000078429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA11	ENST00000078429.9	c.*2458C>T		3_prime_UTR_variant	7/7	1	NM_002067.5	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46385 AN: 151934 Hom.: 7491 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.309 AC: 24969 AN: 80796 Hom.: 4076 Cov.: 0 AF XY: 0.311 AC XY: 11559 AN XY: 37142

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.305 AC: 46398 AN: 152052 Hom.: 7495 Cov.: 33 AF XY: 0.305 AC XY: 22668 AN XY: 74344

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.317

Alfa AF: 0.318 Hom.: 3342

Bravo AF: 0.293

Asia WGS AF: 0.169 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8092; hg19: chr19-3123635;