rs1049583

Variant names:

• chr22-31956804-G-A
• rs1049583
• NM_003405.4:c.*12G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-31956804-G-A
• chr22-31956804-G-T

Variant summary

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

The NM_003405.4(YWHAH):​c.*12G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,565,662 control chromosomes in the GnomAD database, including 74,632 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 0.24 (5418 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69214 hom.)
• Consequence: YWHAH NM_003405.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 26 publications found

Genes affected

YWHAH (HGNC:12853): (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta) 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 bovine orthologs. This gene contains a 7 bp repeat sequence in its 5' UTR, and changes in the number of this repeat have been associated with early-onset schizophrenia and psychotic bipolar disorder. [provided by RefSeq, Jun 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003405.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAH	NM_003405.4	MANE Select	c.*12G>A		3_prime_UTR	Exon 2 of 2	NP_003396.1	Q04917

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YWHAH	ENST00000248975.6	TSL:1 MANE Select	c.*12G>A		3_prime_UTR	Exon 2 of 2	ENSP00000248975.5	Q04917
	YWHAH	ENST00000946727.1		c.*12G>A		3_prime_UTR	Exon 5 of 5	ENSP00000616786.1
	YWHAH	ENST00000397492.1	TSL:3	c.*649G>A		3_prime_UTR	Exon 3 of 3	ENSP00000380629.1	A2IDB1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36484 AN: 151980 Hom.: 5411 Cov.: 32

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.256

GnomAD2 exomes AF: 0.291 AC: 53306 AN: 183110 AF XY: 0.296

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.154

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.308 AC: 434890 AN: 1413564 Hom.: 69214 Cov.: 34 AF XY: 0.307 AC XY: 214767 AN XY: 698720

African (AFR) AF: 0.0635 AC: 2051 AN: 32292

American (AMR) AF: 0.334 AC: 12585 AN: 37662

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 7977 AN: 24486

East Asian (EAS) AF: 0.119 AC: 4421 AN: 37246

South Asian (SAS) AF: 0.289 AC: 23159 AN: 80190

European-Finnish (FIN) AF: 0.301 AC: 15051 AN: 50020

Middle Eastern (MID) AF: 0.293 AC: 1655 AN: 5652

European-Non Finnish (NFE) AF: 0.323 AC: 350767 AN: 1087374

Other (OTH) AF: 0.294 AC: 17224 AN: 58642

GnomAD4 genome AF: 0.240 AC: 36503 AN: 152098 Hom.: 5418 Cov.: 32 AF XY: 0.242 AC XY: 18002 AN XY: 74366

African (AFR) AF: 0.0718 AC: 2980 AN: 41516

American (AMR) AF: 0.302 AC: 4620 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1165 AN: 3468

East Asian (EAS) AF: 0.142 AC: 733 AN: 5170

South Asian (SAS) AF: 0.284 AC: 1370 AN: 4822

European-Finnish (FIN) AF: 0.299 AC: 3161 AN: 10586

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21560 AN: 67948

Other (OTH) AF: 0.258 AC: 544 AN: 2110

Alfa AF: 0.260 Hom.: 2250

Bravo AF: 0.230

Asia WGS AF: 0.220 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1049583; hg19: chr22-32352791; COSMIC: COSV50708718; COSMIC: COSV50708718;