rs1122821

Positions:

• chr19-18940148-A-G
• chr19-18940148-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000542541.6(HOMER3):​c.-365T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,468 control chromosomes in the GnomAD database, including 10,553 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 0.35 (10513 hom., cov: 32)
  • Exomes 𝑓: 0.40 (40 hom.)
• Consequence: HOMER3 ENST00000542541.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

Genes affected

HOMER3 (HGNC:17514): (homer scaffold protein 3) This gene encodes a member of the HOMER family of postsynaptic density scaffolding proteins that share a similar domain structure consisting of an N-terminal Enabled/vasodilator-stimulated phosphoprotein homology 1 domain which mediates protein-protein interactions, and a carboxy-terminal coiled-coil domain and two leucine zipper motifs that are involved in self-oligomerization. The encoded protein binds numerous other proteins including group I metabotropic glutamate receptors, inositol 1,4,5-trisphosphate receptors and amyloid precursor proteins and has been implicated in diverse biological functions such as neuronal signaling, T-cell activation and trafficking of amyloid beta peptides. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER3	NM_004838.4	c.-68+903T>C		intron_variant		ENST00000392351.8
HOMER3	NM_001145722.2	c.-365T>C		5_prime_UTR_variant	1/10
HOMER3	NM_001145721.1	c.-68+173T>C		intron_variant
HOMER3	XM_047439733.1	c.-68+173T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER3	ENST00000392351.8	c.-68+903T>C		intron_variant		1	NM_004838.4	P4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53096 AN: 151960 Hom.: 10521 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.403 AC: 157 AN: 390 Hom.: 40 Cov.: 0 AF XY: 0.351 AC XY: 94 AN XY: 268

Gnomad4 AFR exome AF: 0.700

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.349 AC: 53084 AN: 152078 Hom.: 10513 Cov.: 32 AF XY: 0.350 AC XY: 26026 AN XY: 74362

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.327

Alfa AF: 0.413 Hom.: 13359

Bravo AF: 0.326

Asia WGS AF: 0.286 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1122821; hg19: chr19-19050957;