Variant chr15-82849543-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004839.4(HOMER2):c.*172C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 606,058 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 38 hom. )

Consequence

HOMER2
NM_004839.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.128

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 15-82849543-G-A is Benign according to our data. Variant chr15-82849543-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1320602.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00619 (2810/453766) while in subpopulation SAS AF= 0.017 (711/41766). AF 95% confidence interval is 0.016. There are 38 homozygotes in gnomad4_exome. There are 1618 alleles in male gnomad4_exome subpopulation. Median coverage is 5. This position pass quality control queck.

BS2

High AC in GnomAd4 at 703 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOMER2	NM_004839.4 linkuse as main transcript	c.*172C>T		3_prime_UTR_variant	9/9	ENST00000450735.7	NP_004830.2	Q9NSB8-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HOMER2	ENST00000450735 linkuse as main transcript	c.*172C>T	3_prime_UTR_variant	9/9	1	NM_004839.4	ENSP00000407634.2	Q9NSB8-2
HOMER2	ENST00000558090.2 linkuse as main transcript	c.*26+146C>T	intron_variant		1		ENSP00000452870.1
HOMER2	ENST00000304231 linkuse as main transcript	c.*172C>T	3_prime_UTR_variant	9/9	5		ENSP00000305632.8	Q9NSB8-1

Frequencies

GnomAD3 genomes

AF:

0.00461

AC:

702

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00388

Gnomad OTH

AF:

0.00287

GnomAD4 exome

AF:

0.00619

AC:

2810

AN:

453766

Hom.:

Cov.:

AF XY:

0.00683

AC XY:

1618

AN XY:

236754

show subpopulations

Gnomad4 AFR exome

AF:

0.000476

Gnomad4 AMR exome

AF:

0.000390

Gnomad4 ASJ exome

AF:

0.000220

Gnomad4 EAS exome

AF:

0.0000974

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0257

Gnomad4 NFE exome

AF:

0.00418

Gnomad4 OTH exome

AF:

0.00494

GnomAD4 genome

AF:

0.00462

AC:

703

AN:

152292

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

442

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.0298

Gnomad4 NFE

AF:

0.00388

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00350

Hom.:

Bravo

AF:

0.00175

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.2

DANN

Benign

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over