rs373685350

Variant names:

• chr3-4983309-C-G
• NM_003670.3:c.856C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-4983309-C-G
• chr3-4983309-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003670.3(BHLHE40):​c.856C>G​(p.Pro286Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BHLHE40 NM_003670.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80

Genes affected

BHLHE40 (HGNC:1046): (basic helix-loop-helix family member e40) This gene encodes a basic helix-loop-helix protein expressed in various tissues. The encoded protein can interact with ARNTL or compete for E-box binding sites in the promoter of PER1 and repress CLOCK/ARNTL's transactivation of PER1. This gene is believed to be involved in the control of circadian rhythm and cell differentiation. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21338025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BHLHE40	NM_003670.3	c.856C>G	p.Pro286Ala	missense_variant	Exon 5 of 5	ENST00000256495.4	NP_003661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BHLHE40	ENST00000256495.4	c.856C>G	p.Pro286Ala	missense_variant	Exon 5 of 5	1	NM_003670.3	ENSP00000256495.3
BHLHE40	ENST00000467610.1	n.*41C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.27
Sift	Benign	0.28	T
Sift4G	Benign	1.0	T
Polyphen		0.88	P
Vest4		0.22
MutPred		0.16		Loss of glycosylation at P286 (P = 0.0062);
MVP		0.42
MPC		0.30
ClinPred		0.72	D
GERP RS		5.6
Varity_R		0.058
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-5024994;