19-3119186-T-G

Variant names:

• chr19-3119186-T-G
• rs308046
• NM_002067.5:c.736-20T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002067.5(GNA11):​c.736-20T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,611,764 control chromosomes in the GnomAD database, including 582,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51932 hom., cov: 31)
  • Exomes 𝑓: 0.85 (530768 hom.)
• Consequence: GNA11 NM_002067.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.805
• Publications: 14 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

ENSG00000267139 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-3119186-T-G is Benign according to our data. Variant chr19-3119186-T-G is described in ClinVar as Benign. ClinVar VariationId is 258547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.87 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	NM_002067.5	MANE Select	c.736-20T>G		intron	N/A	NP_002058.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	ENST00000078429.9	TSL:1 MANE Select	c.736-20T>G		intron	N/A	ENSP00000078429.3
	GNA11	ENST00000590534.1	TSL:2	n.2037T>G		non_coding_transcript_exon	Exon 1 of 2
	GNA11	ENST00000587636.1	TSL:5	c.280-20T>G		intron	N/A	ENSP00000465935.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125230 AN: 151934 Hom.: 51891 Cov.: 31

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.840

GnomAD2 exomes AF: 0.839 AC: 209864 AN: 250074 AF XY: 0.835

Gnomad AFR exome AF: 0.729

Gnomad AMR exome AF: 0.906

Gnomad ASJ exome AF: 0.850

Gnomad EAS exome AF: 0.762

Gnomad FIN exome AF: 0.874

Gnomad NFE exome AF: 0.867

Gnomad OTH exome AF: 0.855

GnomAD4 exome AF: 0.852 AC: 1243235 AN: 1459712 Hom.: 530768 Cov.: 42 AF XY: 0.849 AC XY: 616424 AN XY: 726100

African (AFR) AF: 0.736 AC: 24611 AN: 33440

American (AMR) AF: 0.905 AC: 40414 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 22057 AN: 26018

East Asian (EAS) AF: 0.795 AC: 31536 AN: 39682

South Asian (SAS) AF: 0.741 AC: 63805 AN: 86144

European-Finnish (FIN) AF: 0.876 AC: 46482 AN: 53090

Middle Eastern (MID) AF: 0.857 AC: 4934 AN: 5756

European-Non Finnish (NFE) AF: 0.863 AC: 958488 AN: 1110586

Other (OTH) AF: 0.844 AC: 50908 AN: 60316

GnomAD4 genome AF: 0.824 AC: 125330 AN: 152052 Hom.: 51932 Cov.: 31 AF XY: 0.822 AC XY: 61101 AN XY: 74320

African (AFR) AF: 0.737 AC: 30552 AN: 41444

American (AMR) AF: 0.883 AC: 13502 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2960 AN: 3470

East Asian (EAS) AF: 0.759 AC: 3889 AN: 5126

South Asian (SAS) AF: 0.748 AC: 3598 AN: 4812

European-Finnish (FIN) AF: 0.873 AC: 9257 AN: 10606

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58919 AN: 67990

Other (OTH) AF: 0.837 AC: 1763 AN: 2106

Alfa AF: 0.843 Hom.: 5926

Bravo AF: 0.824

Asia WGS AF: 0.764 AC: 2660 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.42
PhyloP100		-0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs308046; hg19: chr19-3119184;