rs2046071

chr15-82838299-G-A

Variant summary

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

The ENST00000558090.2(HOMER2):c.*8975C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,224 control chromosomes in the GnomAD database, including 17,264 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 0.47 (17244 hom., cov: 33)
  • Exomes 𝑓: 0.46 (20 hom.)
• Consequence: HOMER2 ENST00000558090.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

HOMER2 (HGNC:17513): (homer scaffold protein 2) This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. The encoded protein is a postsynaptic density scaffolding protein. Alternative splicing results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 14. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER2	XM_011522232.3	c.*27-505C>T		intron_variant
HOMER2	XM_047433356.1	c.*27-505C>T		intron_variant
HOMER2	XM_047433359.1	c.*27-505C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER2	ENST00000558090.2	c.*8975C>T		3_prime_UTR_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71160 AN: 151930 Hom.: 17227 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.460 AC: 81 AN: 176 Hom.: 20 Cov.: 0 AF XY: 0.424 AC XY: 56 AN XY: 132

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.468 AC: 71228 AN: 152048 Hom.: 17244 Cov.: 33 AF XY: 0.464 AC XY: 34521 AN XY: 74350

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.479

Alfa AF: 0.506 Hom.: 40647

Bravo AF: 0.464

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.5
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2046071; hg19: chr15-83507051;