9-77451154-A-G

Position:

• chr9-77451154-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004297.4(GNA14):​c.310-16632T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,052 control chromosomes in the GnomAD database, including 4,673 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 0.23 (4673 hom., cov: 32)
• Consequence: GNA14 NM_004297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

Genes affected

GNA14 (HGNC:4382): (G protein subunit alpha 14) This gene encodes a member of the guanine nucleotide-binding, or G protein family. G proteins are heterotrimers consisting of alpha, beta and gamma subunits. The encoded protein is a member of the alpha family of G proteins, more specifically the alpha q subfamily of G proteins. The encoded protein may play a role in pertussis-toxin resistant activation of phospholipase C-beta and its downstream effectors.[provided by RefSeq, Feb 2009]

GNA14-AS1 (HGNC:50451): (GNA14 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNA14	NM_004297.4	c.310-16632T>C		intron_variant		ENST00000341700.7	NP_004288.1
GNA14	XM_047424110.1	c.-3896T>C		5_prime_UTR_premature_start_codon_gain_variant	1/6		XP_047280066.1
GNA14	XM_047424110.1	c.-3896T>C		5_prime_UTR_variant	1/6		XP_047280066.1
GNA14-AS1	NR_121184.1	n.33+3473A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNA14	ENST00000341700.7	c.310-16632T>C		intron_variant		1	NM_004297.4	ENSP00000365807.4

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34881 AN: 151934 Hom.: 4677 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.230 AC: 34914 AN: 152052 Hom.: 4673 Cov.: 32 AF XY: 0.236 AC XY: 17537 AN XY: 74346

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.229

Alfa AF: 0.167 Hom.: 3719

Bravo AF: 0.242

Asia WGS AF: 0.308 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.61

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: rs4745639; hg19: chr9-80066070;