Variant 8-64581450-T-TAGCGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_152414.5(BHLHE22):c.667_672dup(p.Ser223_Gly224dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 1,525,034 control chromosomes in the GnomAD database, including 6,370 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G220G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.092 ( 634 hom., cov: 31)

Exomes 𝑓: 0.096 ( 5736 hom. )

Consequence

BHLHE22
NM_152414.5 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.262

Variant links:

Genes affected

BHLHE22 (HGNC:11963): (basic helix-loop-helix family member e22) This gene encodes a protein that belongs to the basic helix-loop-helix (bHLH) family of transcription factors that regulate cell fate determination, proliferation, and differentiation. A similar protein in mouse is required for the development of the dorsal cochlear nuclei, and is thought to play a role in in the differentiation of neurons involved in sensory input. The mouse protein also functions in retinogenesis. [provided by RefSeq, Oct 2016]

BHLHE22 links:

BHLHE22-AS1 (HGNC:56147): (BHLHE22 antisense RNA 1)

BHLHE22-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 8-64581450-T-TAGCGGC is Benign according to our data. Variant chr8-64581450-T-TAGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 218845.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHLHE22	NM_152414.5 linkuse as main transcript	c.667_672dup	p.Ser223_Gly224dup	inframe_insertion	1/1	ENST00000321870.3
BHLHE22-AS1	NR_152770.1 linkuse as main transcript	n.175+267_175+268insGCCGCT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BHLHE22	ENST00000321870.3 linkuse as main transcript	c.667_672dup	p.Ser223_Gly224dup	inframe_insertion	1/1		NM_152414.5	P1
BHLHE22-AS1	ENST00000517909.1 linkuse as main transcript	n.171+267_171+268insGCCGCT		intron_variant, non_coding_transcript_variant		2
BHLHE22-AS1	ENST00000665275.1 linkuse as main transcript	n.94+267_94+268insGCCGCT		intron_variant, non_coding_transcript_variant
BHLHE22-AS1	ENST00000670034.1 linkuse as main transcript	n.204+267_204+268insGCCGCT		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0916

AC:

13791

AN:

150518

Hom.:

632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0700

Gnomad AMI

AF:

0.0668

Gnomad AMR

AF:

0.0721

Gnomad ASJ

AF:

0.0882

Gnomad EAS

AF:

0.00390

Gnomad SAS

AF:

0.0375

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.103

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.0911

GnomAD3 exomes

AF:

0.0684

AC:

9059

AN:

132494

Hom.:

357

AF XY:

0.0666

AC XY:

4838

AN XY:

72634

show subpopulations

Gnomad AFR exome

AF:

0.0618

Gnomad AMR exome

AF:

0.0475

Gnomad ASJ exome

AF:

0.0739

Gnomad EAS exome

AF:

0.00331

Gnomad SAS exome

AF:

0.0369

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0990

Gnomad OTH exome

AF:

0.0840

GnomAD4 exome

AF:

0.0962

AC:

132184

AN:

1374408

Hom.:

5736

Cov.:

AF XY:

0.0947

AC XY:

64263

AN XY:

678848

show subpopulations

Gnomad4 AFR exome

AF:

0.0635

Gnomad4 AMR exome

AF:

0.0512

Gnomad4 ASJ exome

AF:

0.0806

Gnomad4 EAS exome

AF:

0.00151

Gnomad4 SAS exome

AF:

0.0385

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.106

Gnomad4 OTH exome

AF:

0.0844

GnomAD4 genome

AF:

0.0917

AC:

13809

AN:

150626

Hom.:

634

Cov.:

AF XY:

0.0919

AC XY:

6763

AN XY:

73624

show subpopulations

Gnomad4 AFR

AF:

0.0702

Gnomad4 AMR

AF:

0.0720

Gnomad4 ASJ

AF:

0.0882

Gnomad4 EAS

AF:

0.00391

Gnomad4 SAS

AF:

0.0375

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.0906

Alfa

AF:

0.0649

Hom.:

Asia WGS

AF:

0.0260

AC:

AN:

3450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jun 19, 2015

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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