rs17360083

Variant names:

• chr15-82901329-C-A
• rs17360083
• NM_004839.4:c.6-8488G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-82901329-C-A
• chr15-82901329-C-T

Variant summary

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

The NM_004839.4(HOMER2):​c.6-8488G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,034 control chromosomes in the GnomAD database, including 11,205 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 0.37 (11205 hom., cov: 32)
• Consequence: HOMER2 NM_004839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 4 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

ENSG00000308606 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER2	NM_004839.4	c.6-8488G>T		intron_variant	Intron 1 of 8	ENST00000450735.7	NP_004830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER2	ENST00000450735.7	c.6-8488G>T		intron_variant	Intron 1 of 8	1	NM_004839.4	ENSP00000407634.2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55854 AN: 151918 Hom.: 11206 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.367 AC: 55864 AN: 152034 Hom.: 11205 Cov.: 32 AF XY: 0.366 AC XY: 27199 AN XY: 74322

African (AFR) AF: 0.214 AC: 8887 AN: 41464

American (AMR) AF: 0.372 AC: 5682 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1459 AN: 3462

East Asian (EAS) AF: 0.165 AC: 850 AN: 5164

South Asian (SAS) AF: 0.462 AC: 2222 AN: 4814

European-Finnish (FIN) AF: 0.448 AC: 4737 AN: 10578

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30669 AN: 67976

Other (OTH) AF: 0.376 AC: 791 AN: 2106

Alfa AF: 0.358 Hom.: 2275

Bravo AF: 0.354

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.8
DANN	Benign	0.79
PhyloP100		-0.19
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: rs17360083; hg19: chr15-83570081;