8-64580797-C-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_152414.5(BHLHE22):c.7C>A(p.Arg3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,384,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000034 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
BHLHE22
NM_152414.5 missense
NM_152414.5 missense
Scores
7
3
9
Clinical Significance
Conservation
PhyloP100: 1.47
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.05318719).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BHLHE22 | NM_152414.5 | c.7C>A | p.Arg3Ser | missense_variant | 1/1 | ENST00000321870.3 | |
BHLHE22-AS1 | NR_152770.1 | n.175+921G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BHLHE22 | ENST00000321870.3 | c.7C>A | p.Arg3Ser | missense_variant | 1/1 | NM_152414.5 | P1 | ||
BHLHE22-AS1 | ENST00000517909.1 | n.171+921G>T | intron_variant, non_coding_transcript_variant | 2 | |||||
BHLHE22-AS1 | ENST00000665275.1 | n.94+921G>T | intron_variant, non_coding_transcript_variant | ||||||
BHLHE22-AS1 | ENST00000670034.1 | n.204+921G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000341 AC: 5AN: 146678Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000532 AC: 3AN: 56426Hom.: 0 AF XY: 0.0000612 AC XY: 2AN XY: 32698
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GnomAD4 exome AF: 0.0000154 AC: 19AN: 1237744Hom.: 0 Cov.: 31 AF XY: 0.0000181 AC XY: 11AN XY: 607594
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GnomAD4 genome AF: 0.0000341 AC: 5AN: 146678Hom.: 0 Cov.: 31 AF XY: 0.0000419 AC XY: 3AN XY: 71552
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 08, 2022 | The c.7C>A (p.R3S) alteration is located in exon 1 (coding exon 1) of the BHLHE22 gene. This alteration results from a C to A substitution at nucleotide position 7, causing the arginine (R) at amino acid position 3 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Gain of glycosylation at R3 (P = 0.0112);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at