rs8092

Variant names:

• chr19-3123637-C-T
• rs8092
• NM_002067.5:c.*2458C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

GNA11 Gene-Disease associations (from GenCC):

• autosomal dominant hypocalcemia 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital hemangioma

  Inheritance: AD Classification: STRONG Submitted by: G2P
• familial hypocalciuric hypercalcemia 2

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant hypocalcemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002067.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	NM_002067.5	MANE Select	c.*2458C>T		3_prime_UTR	Exon 7 of 7	NP_002058.2	P29992

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	ENST00000078429.9	TSL:1 MANE Select	c.*2458C>T		3_prime_UTR	Exon 7 of 7	ENSP00000078429.3	P29992

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

African (AFR) AF: 0.226 AC: 878 AN: 3884

American (AMR) AF: 0.239 AC: 596 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1911 AN: 5112

East Asian (EAS) AF: 0.187 AC: 2127 AN: 11392

South Asian (SAS) AF: 0.148 AC: 104 AN: 704

European-Finnish (FIN) AF: 0.483 AC: 28 AN: 58

Middle Eastern (MID) AF: 0.336 AC: 166 AN: 494

European-Non Finnish (NFE) AF: 0.342 AC: 17044 AN: 49898

Other (OTH) AF: 0.313 AC: 2115 AN: 6758

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

African (AFR) AF: 0.240 AC: 9956 AN: 41456

American (AMR) AF: 0.256 AC: 3908 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1305 AN: 3468

East Asian (EAS) AF: 0.194 AC: 997 AN: 5150

South Asian (SAS) AF: 0.182 AC: 880 AN: 4826

European-Finnish (FIN) AF: 0.434 AC: 4594 AN: 10584

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23612 AN: 67960

Other (OTH) AF: 0.317 AC: 671 AN: 2116

Alfa AF: 0.319 Hom.: 4184

Bravo AF: 0.293

Asia WGS AF: 0.169 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.70
PhyloP100		0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8092; hg19: chr19-3123635;