NM_004272.5:c.294+114G>A

Variant names:

• chr5-79450876-C-T
• rs13356332
• NM_004272.5:c.294+114G>A

Variant summary

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

The NM_004272.5(HOMER1):​c.294+114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,041,592 control chromosomes in the GnomAD database, including 39,023 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 0.26 (5366 hom., cov: 32)
  • Exomes 𝑓: 0.27 (33657 hom.)
• Consequence: HOMER1 NM_004272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.780
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER1	NM_004272.5	c.294+114G>A		intron_variant	Intron 3 of 8	ENST00000334082.11	NP_004263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER1	ENST00000334082.11	c.294+114G>A		intron_variant	Intron 3 of 8	1	NM_004272.5	ENSP00000334382.6
HOMER1	ENST00000282260.10	c.294+114G>A		intron_variant	Intron 3 of 5	1		ENSP00000282260.6
HOMER1	ENST00000535690.1	c.6-48821G>A		intron_variant	Intron 1 of 4	1		ENSP00000441587.1
HOMER1	ENST00000508576.5	c.294+114G>A		intron_variant	Intron 3 of 5	1		ENSP00000426651.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39902 AN: 151908 Hom.: 5356 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.271 AC: 240840 AN: 889566 Hom.: 33657 AF XY: 0.274 AC XY: 121421 AN XY: 442946

African (AFR) AF: 0.264 AC: 5561 AN: 21034

American (AMR) AF: 0.225 AC: 4992 AN: 22194

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 6093 AN: 16850

East Asian (EAS) AF: 0.163 AC: 5322 AN: 32746

South Asian (SAS) AF: 0.373 AC: 17395 AN: 46688

European-Finnish (FIN) AF: 0.218 AC: 7046 AN: 32342

Middle Eastern (MID) AF: 0.363 AC: 1479 AN: 4076

European-Non Finnish (NFE) AF: 0.270 AC: 182005 AN: 673752

Other (OTH) AF: 0.274 AC: 10947 AN: 39884

GnomAD4 genome AF: 0.263 AC: 39942 AN: 152026 Hom.: 5366 Cov.: 32 AF XY: 0.264 AC XY: 19609 AN XY: 74298

African (AFR) AF: 0.261 AC: 10828 AN: 41480

American (AMR) AF: 0.255 AC: 3894 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3468

East Asian (EAS) AF: 0.145 AC: 750 AN: 5178

South Asian (SAS) AF: 0.372 AC: 1793 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2192 AN: 10530

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18459 AN: 67958

Other (OTH) AF: 0.287 AC: 605 AN: 2110

Alfa AF: 0.165 Hom.: 319

Bravo AF: 0.260

Asia WGS AF: 0.296 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.77
PhyloP100		0.78
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: rs13356332; hg19: chr5-78746699; COSMIC: COSV107282870;