rs4820537

Variant names:

• chr22-23122623-G-A
• rs4820537
• NM_002073.4:c.724-464G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-23122623-G-A
• chr22-23122623-G-C

Variant summary

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

The NM_002073.4(GNAZ):​c.724-464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 168,026 control chromosomes in the GnomAD database, including 14,753 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 0.40 (13132 hom., cov: 32)
  • Exomes 𝑓: 0.43 (1621 hom.)
• Consequence: GNAZ NM_002073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

Genes affected

GNAZ (HGNC:4395): (G protein subunit alpha z) The protein encoded by this gene is a member of a G protein subfamily that mediates signal transduction in pertussis toxin-insensitive systms. This encoded protein may play a role in maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluids. [provided by RefSeq, Jul 2008]

RSPH14 (HGNC:13437): (radial spoke head 14 homolog) This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAZ	NM_002073.4	c.724-464G>A		intron_variant	Intron 2 of 2	ENST00000615612.2	NP_002064.1
RSPH14	NM_014433.3	c.421+11403C>T		intron_variant	Intron 4 of 6	ENST00000216036.9	NP_055248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAZ	ENST00000615612.2	c.724-464G>A		intron_variant	Intron 2 of 2	1	NM_002073.4	ENSP00000478892.1
RSPH14	ENST00000216036.9	c.421+11403C>T		intron_variant	Intron 4 of 6	1	NM_014433.3	ENSP00000216036.4
GNAZ	ENST00000479571.1	n.246G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60755 AN: 151986 Hom.: 13135 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.432 AC: 6878 AN: 15922 Hom.: 1621 Cov.: 0 AF XY: 0.429 AC XY: 3594 AN XY: 8368

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.400 AC: 60779 AN: 152104 Hom.: 13132 Cov.: 32 AF XY: 0.399 AC XY: 29662 AN XY: 74348

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.419

Alfa AF: 0.471 Hom.: 22408

Bravo AF: 0.395

Asia WGS AF: 0.381 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.75

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: rs4820537; hg19: chr22-23464810;