rs777622556

Variant names:

• chr8-64581308-C-T
• rs777622556
• NM_152414.5:c.518C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-64581308-C-T
• chr8-64581308-C-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152414.5(BHLHE22):​c.518C>T​(p.Ala173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000671 in 1,429,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: BHLHE22 NM_152414.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.363
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.061368734).
• BS2: High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152414.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHLHE22	NM_152414.5	MANE Select	c.518C>T	p.Ala173Val	missense	Exon 1 of 1	NP_689627.1	Q8NFJ8
	BHLHE22-AS1	NR_152770.1		n.175+410G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHLHE22	ENST00000321870.3	TSL:6 MANE Select	c.518C>T	p.Ala173Val	missense	Exon 1 of 1	ENSP00000318799.1	Q8NFJ8
	BHLHE22-AS1	ENST00000517909.1	TSL:2	n.171+410G>A		intron	N/A
	BHLHE22-AS1	ENST00000665275.1		n.94+410G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000661 AC: 10 AN: 151360 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000274 AC: 10 AN: 36506 AF XY: 0.000377

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000352

Gnomad FIN exome AF: 0.000516

Gnomad NFE exome AF: 0.000424

Gnomad OTH exome AF: 0.000967

GnomAD4 exome AF: 0.0000673 AC: 86 AN: 1278288 Hom.: 0 Cov.: 35 AF XY: 0.0000686 AC XY: 43 AN XY: 626646

African (AFR) AF: 0.00 AC: 0 AN: 25502

American (AMR) AF: 0.00 AC: 0 AN: 16534

Ashkenazi Jewish (ASJ) AF: 0.0000529 AC: 1 AN: 18908

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30084

South Asian (SAS) AF: 0.00 AC: 0 AN: 62210

European-Finnish (FIN) AF: 0.0000970 AC: 3 AN: 30912

Middle Eastern (MID) AF: 0.000232 AC: 1 AN: 4304

European-Non Finnish (NFE) AF: 0.0000752 AC: 78 AN: 1036936

Other (OTH) AF: 0.0000378 AC: 2 AN: 52898

GnomAD4 genome AF: 0.0000661 AC: 10 AN: 151360 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 73952

African (AFR) AF: 0.00 AC: 0 AN: 41194

American (AMR) AF: 0.0000656 AC: 1 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5016

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67858

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000693 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.000165 AC: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.59	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.36
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.25
Sift	Uncertain	0.013	D
Sift4G	Benign	0.39	T
Polyphen		0.18	B
Vest4		0.13
MutPred		0.24		Gain of relative solvent accessibility (P = 0.005)
MVP		0.19
MPC		1.0
ClinPred		0.041	T
GERP RS		2.6
Varity_R		0.11
gMVP		0.23
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs777622556; hg19: chr8-65493865;