3-4983135-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003670.3(BHLHE40):c.682G>A(p.Ala228Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003670.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BHLHE40 | NM_003670.3 | c.682G>A | p.Ala228Thr | missense_variant | 5/5 | ENST00000256495.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BHLHE40 | ENST00000256495.4 | c.682G>A | p.Ala228Thr | missense_variant | 5/5 | 1 | NM_003670.3 | P1 | |
BHLHE40 | ENST00000467610.1 | n.1233G>A | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251162Hom.: 0 AF XY: 0.0000958 AC XY: 13AN XY: 135768
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461796Hom.: 0 Cov.: 34 AF XY: 0.0000468 AC XY: 34AN XY: 727194
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2022 | The c.682G>A (p.A228T) alteration is located in exon 5 (coding exon 5) of the BHLHE40 gene. This alteration results from a G to A substitution at nucleotide position 682, causing the alanine (A) at amino acid position 228 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at