chr19-3095929-T-C

Variant names:

• chr19-3095929-T-C
• rs308039
• NM_002067.5:c.136+1142T>C

Variant summary

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

The NM_002067.5(GNA11):​c.136+1142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,018 control chromosomes in the GnomAD database, including 39,990 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 0.72 (39990 hom., cov: 31)
• Consequence: GNA11 NM_002067.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• congenital hemangioma

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

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNA11	NM_002067.5	c.136+1142T>C		intron_variant	Intron 1 of 6	ENST00000078429.9	NP_002058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNA11	ENST00000078429.9	c.136+1142T>C		intron_variant	Intron 1 of 6	1	NM_002067.5	ENSP00000078429.3
GNA11	ENST00000586763.1	n.139+1142T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108757 AN: 151900 Hom.: 39974 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.716 AC: 108813 AN: 152018 Hom.: 39990 Cov.: 31 AF XY: 0.711 AC XY: 52820 AN XY: 74298

African (AFR) AF: 0.569 AC: 23573 AN: 41450

American (AMR) AF: 0.665 AC: 10166 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2739 AN: 3472

East Asian (EAS) AF: 0.589 AC: 3020 AN: 5124

South Asian (SAS) AF: 0.541 AC: 2603 AN: 4812

European-Finnish (FIN) AF: 0.838 AC: 8874 AN: 10588

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55449 AN: 67982

Other (OTH) AF: 0.726 AC: 1531 AN: 2108

Alfa AF: 0.767 Hom.: 30435

Bravo AF: 0.702

Asia WGS AF: 0.561 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.69
PhyloP100		0.31
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: rs308039; hg19: chr19-3095927;