dbSNP rs1122821: HOMER3:c.-365T>C (chr19-18940148-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000542541.6(HOMER3):c.-365T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,468 control chromosomes in the GnomAD database, including 10,553 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 0.35 ( 10513 hom., cov: 32)

Exomes 𝑓: 0.40 ( 40 hom. )

Consequence

HOMER3
ENST00000542541.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

15 publications found

Variant links:

Genes affected

HOMER3 (HGNC:17514): (homer scaffold protein 3) This gene encodes a member of the HOMER family of postsynaptic density scaffolding proteins that share a similar domain structure consisting of an N-terminal Enabled/vasodilator-stimulated phosphoprotein homology 1 domain which mediates protein-protein interactions, and a carboxy-terminal coiled-coil domain and two leucine zipper motifs that are involved in self-oligomerization. The encoded protein binds numerous other proteins including group I metabotropic glutamate receptors, inositol 1,4,5-trisphosphate receptors and amyloid precursor proteins and has been implicated in diverse biological functions such as neuronal signaling, T-cell activation and trafficking of amyloid beta peptides. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

HOMER3 links:

HOMER3-AS1 (HGNC:53775): (HOMER3 antisense RNA 1)

HOMER3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOMER3	NM_004838.4 link	c.-68+903T>C		intron_variant	Intron 1 of 9	ENST00000392351.8	NP_004829.3	Q9NSC5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOMER3	ENST00000392351.8 link	c.-68+903T>C		intron_variant	Intron 1 of 9	1	NM_004838.4	ENSP00000376162.2		Q9NSC5-1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53096

AN:

151960

Hom.:

10521

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.483

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.441

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.403

AC:

157

AN:

390

Hom.:

Cov.:

AF XY:

0.351

AC XY:

AN XY:

268

show subpopulations

African (AFR)

AF:

0.700

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.417

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.395

AC:

136

AN:

344

Other (OTH)

AF:

0.429

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.349

AC:

53084

AN:

152078

Hom.:

10513

Cov.:

AF XY:

0.350

AC XY:

26026

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.169

AC:

7035

AN:

41530

American (AMR)

AF:

0.298

AC:

4553

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1200

AN:

3468

East Asian (EAS)

AF:

0.400

AC:

2060

AN:

5150

South Asian (SAS)

AF:

0.295

AC:

1425

AN:

4824

European-Finnish (FIN)

AF:

0.531

AC:

5620

AN:

10592

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.441

AC:

29967

AN:

67930

Other (OTH)

AF:

0.327

AC:

690

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1675

3350

5024

6699

8374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.407

Hom.:

17346

Bravo

AF:

0.326

Asia WGS

AF:

0.286

AC:

994

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.073

PromoterAI

-0.033

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs1122821

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over