8-64581445-A-G

Position:

• chr8-64581445-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152414.5(BHLHE22):​c.655A>G​(p.Ser219Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000505 in 1,386,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: BHLHE22 NM_152414.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03271666).
• BP6: Variant 8-64581445-A-G is Benign according to our data. Variant chr8-64581445-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3260851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHLHE22	NM_152414.5	c.655A>G	p.Ser219Gly	missense_variant	1/1	ENST00000321870.3
BHLHE22-AS1	NR_152770.1	n.175+273T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BHLHE22	ENST00000321870.3	c.655A>G	p.Ser219Gly	missense_variant	1/1		NM_152414.5	P1
BHLHE22-AS1	ENST00000517909.1	n.171+273T>C		intron_variant, non_coding_transcript_variant		2
BHLHE22-AS1	ENST00000665275.1	n.94+273T>C		intron_variant, non_coding_transcript_variant
BHLHE22-AS1	ENST00000670034.1	n.204+273T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000505 AC: 7 AN: 1386154 Hom.: 0 Cov.: 35 AF XY: 0.00000877 AC XY: 6 AN XY: 684440

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000556

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.10
DANN	Benign	0.094
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.15	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.091
Sift	Benign	1.0	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.30		Loss of phosphorylation at S219 (P = 1e-04);
MVP		0.20
MPC		0.88
ClinPred		0.020	T
GERP RS		-3.1
Varity_R		0.027
gMVP		0.63

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

Other links and lift over

dbSNP: rs1585786806; hg19: chr8-65494002;