chr16-23505353-C-T

Variant names:

• chr16-23505353-C-T
• rs739498
• NM_015044.4:c.91+4968G>A

Variant summary

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

The NM_015044.4(GGA2):​c.91+4968G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 152,118 control chromosomes in the GnomAD database, including 579 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 0.046 (579 hom., cov: 32)
• Consequence: GGA2 NM_015044.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 1 publications found

Genes affected

GGA2 (HGNC:16064): (golgi associated, gamma adaptin ear containing, ARF binding protein 2) This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. This family member may play a significant role in cargo molecules regulation and clathrin-coated vesicle assembly. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGA2	NM_015044.4	c.91+4968G>A		intron_variant	Intron 1 of 16	ENST00000309859.8	NP_055859.1
GGA2	XM_047433801.1	c.62-9575G>A		intron_variant	Intron 2 of 17		XP_047289757.1
GGA2	XM_047433802.1	c.-21+3945G>A		intron_variant	Intron 1 of 16		XP_047289758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGA2	ENST00000309859.8	c.91+4968G>A		intron_variant	Intron 1 of 16	1	NM_015044.4	ENSP00000311962.4

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7022 AN: 152000 Hom.: 578 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0462 AC: 7035 AN: 152118 Hom.: 579 Cov.: 32 AF XY: 0.0448 AC XY: 3334 AN XY: 74362

African (AFR) AF: 0.159 AC: 6586 AN: 41448

American (AMR) AF: 0.0196 AC: 299 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.000721 AC: 49 AN: 67986

Other (OTH) AF: 0.0302 AC: 64 AN: 2116

Alfa AF: 0.0549 Hom.: 85

Bravo AF: 0.0523

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.77
PhyloP100		-1.0
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: rs739498; hg19: chr16-23516674;