rs1256428

Variant names:

• chr15-82853066-C-T
• rs1256428
• NM_004839.4:c.652-814G>A

Variant summary

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

The NM_004839.4(HOMER2):​c.652-814G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,074 control chromosomes in the GnomAD database, including 22,907 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 0.55 (22907 hom., cov: 33)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 13 publications found

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]

HOMER2 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 68

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER2	NM_004839.4	c.652-814G>A		intron_variant	Intron 6 of 8	ENST00000450735.7	NP_004830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER2	ENST00000450735.7	c.652-814G>A		intron_variant	Intron 6 of 8	1	NM_004839.4	ENSP00000407634.2
HOMER2	ENST00000304231.12	c.685-814G>A		intron_variant	Intron 6 of 8	5		ENSP00000305632.8
HOMER2	ENST00000558817.1	c.409-814G>A		intron_variant	Intron 3 of 4	3		ENSP00000454125.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82823 AN: 151956 Hom.: 22886 Cov.: 33

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.545 AC: 82890 AN: 152074 Hom.: 22907 Cov.: 33 AF XY: 0.546 AC XY: 40629 AN XY: 74366

African (AFR) AF: 0.627 AC: 26043 AN: 41504

American (AMR) AF: 0.511 AC: 7813 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2705 AN: 5160

South Asian (SAS) AF: 0.501 AC: 2416 AN: 4826

European-Finnish (FIN) AF: 0.528 AC: 5586 AN: 10572

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.511 AC: 34753 AN: 67958

Other (OTH) AF: 0.549 AC: 1158 AN: 2110

Alfa AF: 0.520 Hom.: 41426

Bravo AF: 0.548

Asia WGS AF: 0.559 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.40
PhyloP100		-0.51
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: rs1256428; hg19: chr15-83521818;