chr19-3119241-C-T

Variant names:

• chr19-3119241-C-T
• rs4900
• NM_002067.5:c.771C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002067.5(GNA11):​c.771C>T​(p.Thr257Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,612,358 control chromosomes in the GnomAD database, including 172,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12144 hom., cov: 32)
  • Exomes 𝑓: 0.47 (160274 hom.)
• Consequence: GNA11 NM_002067.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.579
• Publications: 33 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 19-3119241-C-T is Benign according to our data. Variant chr19-3119241-C-T is described in ClinVar as Benign. ClinVar VariationId is 258548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.579 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 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.771C>T	p.Thr257Thr	synonymous	Exon 6 of 7	NP_002058.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNA11	ENST00000078429.9	TSL:1 MANE Select	c.771C>T	p.Thr257Thr	synonymous	Exon 6 of 7	ENSP00000078429.3
	GNA11	ENST00000587636.1	TSL:5	c.315C>T	p.Thr105Thr	synonymous	Exon 4 of 6	ENSP00000465935.1
	GNA11	ENST00000586180.1	TSL:3	n.290C>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58250 AN: 151846 Hom.: 12137 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.395

GnomAD2 exomes AF: 0.427 AC: 107299 AN: 251156 AF XY: 0.431

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.422

Gnomad ASJ exome AF: 0.402

Gnomad EAS exome AF: 0.407

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.436

GnomAD4 exome AF: 0.465 AC: 679315 AN: 1460394 Hom.: 160274 Cov.: 42 AF XY: 0.465 AC XY: 337506 AN XY: 726498

African (AFR) AF: 0.209 AC: 7001 AN: 33440

American (AMR) AF: 0.417 AC: 18650 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10628 AN: 26130

East Asian (EAS) AF: 0.438 AC: 17368 AN: 39690

South Asian (SAS) AF: 0.422 AC: 36249 AN: 85938

European-Finnish (FIN) AF: 0.376 AC: 20037 AN: 53286

Middle Eastern (MID) AF: 0.436 AC: 2515 AN: 5768

European-Non Finnish (NFE) AF: 0.486 AC: 539657 AN: 1111100

Other (OTH) AF: 0.451 AC: 27210 AN: 60334

GnomAD4 genome AF: 0.384 AC: 58289 AN: 151964 Hom.: 12144 Cov.: 32 AF XY: 0.379 AC XY: 28141 AN XY: 74266

African (AFR) AF: 0.216 AC: 8944 AN: 41484

American (AMR) AF: 0.410 AC: 6255 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2118 AN: 5158

South Asian (SAS) AF: 0.421 AC: 2011 AN: 4772

European-Finnish (FIN) AF: 0.368 AC: 3894 AN: 10582

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32414 AN: 67914

Other (OTH) AF: 0.397 AC: 837 AN: 2108

Alfa AF: 0.429 Hom.: 8134

Bravo AF: 0.378

Asia WGS AF: 0.410 AC: 1426 AN: 3478

EpiCase AF: 0.472

EpiControl AF: 0.472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs4900; hg19: chr19-3119239; COSMIC: COSV50020241; COSMIC: COSV50020241;