rs61731116

Positions:

• chr19-3110201-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002067.5(GNA11):​c.189C>T​(p.His63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,613,544 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (39 hom.)
• Consequence: GNA11 NM_002067.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.131

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 19-3110201-C-T is Benign according to our data. Variant chr19-3110201-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.131 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00174 (265/152198) while in subpopulation SAS AF= 0.0217 (105/4828). AF 95% confidence interval is 0.0184. There are 2 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 265 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNA11	NM_002067.5	c.189C>T	p.His63=	synonymous_variant	2/7	ENST00000078429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNA11	ENST00000078429.9	c.189C>T	p.His63=	synonymous_variant	2/7	1	NM_002067.5	P1
GNA11	ENST00000586763.1	n.140-3129C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 264 AN: 152080 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00196

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00304 AC: 759 AN: 249742 Hom.: 8 AF XY: 0.00396 AC XY: 536 AN XY: 135376

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0171

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00182

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00280 AC: 4088 AN: 1461346 Hom.: 39 Cov.: 32 AF XY: 0.00328 AC XY: 2382 AN XY: 726980

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000314

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0187

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.00199

Gnomad4 OTH exome AF: 0.00333

GnomAD4 genome AF: 0.00174 AC: 265 AN: 152198 Hom.: 2 Cov.: 32 AF XY: 0.00185 AC XY: 138 AN XY: 74416

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00154 Hom.: 1

Bravo AF: 0.00122

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00137

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 21, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.3
DANN	Benign	0.72

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: rs61731116; hg19: chr19-3110199;