rs4293896

Positions:

• chr5-79437419-A-C
• chr5-79437419-A-G
• chr5-79437419-A-T

Variant summary

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

The NM_004272.5(HOMER1):​c.527+1591T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,114 control chromosomes in the GnomAD database, including 6,068 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 0.25 (6068 hom., cov: 33)
• Consequence: HOMER1 NM_004272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

Genes affected

HOMER1 (HGNC:17512): (homer scaffold protein 1) This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. [provided by RefSeq, Jul 2008]

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 (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOMER1	NM_004272.5	c.527+1591T>G		intron_variant		ENST00000334082.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOMER1	ENST00000334082.11	c.527+1591T>G		intron_variant		1	NM_004272.5	P1
HOMER1	ENST00000282260.10	c.294+13571T>G		intron_variant		1
HOMER1	ENST00000508576.5	c.527+1591T>G		intron_variant		1
HOMER1	ENST00000535690.1	c.6-35364T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38750 AN: 151994 Hom.: 6061 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.255 AC: 38761 AN: 152114 Hom.: 6068 Cov.: 33 AF XY: 0.263 AC XY: 19562 AN XY: 74370

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.265

Alfa AF: 0.219 Hom.: 517

Bravo AF: 0.276

Asia WGS AF: 0.479 AC: 1653 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.69

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: rs4293896; hg19: chr5-78733242;