rs1256453

Positions:

• chr15-82875096-C-A
• chr15-82875096-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004839.4(HOMER2):​c.294+177G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,088 control chromosomes in the GnomAD database, including 30,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (30203 hom., cov: 32)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.402

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 15-82875096-C-A is Benign according to our data. Variant chr15-82875096-C-A is described in ClinVar as [Benign]. Clinvar id is 1237323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER2	NM_004839.4	c.294+177G>T		intron_variant		ENST00000450735.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER2	ENST00000450735.7	c.294+177G>T		intron_variant		1	NM_004839.4
HOMER2	ENST00000304231.12	c.294+177G>T		intron_variant		5		P1
HOMER2	ENST00000560374.5	n.623+177G>T		intron_variant, non_coding_transcript_variant		3
HOMER2	ENST00000561345.5	n.353+177G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94597 AN: 151970 Hom.: 30158 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.623 AC: 94701 AN: 152088 Hom.: 30203 Cov.: 32 AF XY: 0.625 AC XY: 46418 AN XY: 74328

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.623

Alfa AF: 0.460 Hom.: 1273

Bravo AF: 0.635

Asia WGS AF: 0.696 AC: 2419 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.61

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: rs1256453; hg19: chr15-83543848;