rs1470764

Positions:

• chr8-100937810-G-A
• chr8-100937810-G-C

Variant summary

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

The NM_145690.3(YWHAZ):​c.294+10786C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,042 control chromosomes in the GnomAD database, including 33,227 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 0.66 (33227 hom., cov: 32)
• Consequence: YWHAZ NM_145690.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

Genes affected

YWHAZ (HGNC:12855): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse, rat and sheep orthologs. The encoded protein interacts with IRS1 protein, suggesting a role in regulating insulin sensitivity. Several transcript variants that differ in the 5' UTR but that encode the same protein have been identified for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YWHAZ	NM_145690.3	c.294+10786C>T		intron_variant		ENST00000395958.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YWHAZ	ENST00000395958.6	c.294+10786C>T		intron_variant		1	NM_145690.3	P1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99629 AN: 151918 Hom.: 33198 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.656 AC: 99701 AN: 152042 Hom.: 33227 Cov.: 32 AF XY: 0.651 AC XY: 48412 AN XY: 74310

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.639

Alfa AF: 0.633 Hom.: 9487

Bravo AF: 0.670

Asia WGS AF: 0.643 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.090
DANN	Benign	0.70

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: rs1470764; hg19: chr8-101950038;