12-26120155-C-G

Variant names:

• chr12-26120155-C-G
• rs1048155
• NM_030762.3:c.*1911G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000242728.5(BHLHE41):​c.*1911G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,302 control chromosomes in the GnomAD database, including 21,011 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (20966 hom., cov: 33)
  • Exomes 𝑓: 0.61 (45 hom.)
• Consequence: BHLHE41 ENST00000242728.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 13 publications found

Genes affected

BHLHE41 (HGNC:16617): (basic helix-loop-helix family member e41) 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. Defects in this gene are associated with the short sleep phenotype. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000242728.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHLHE41	NM_030762.3	MANE Select	c.*1911G>C		3_prime_UTR	Exon 5 of 5	NP_110389.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHLHE41	ENST00000242728.5	TSL:1 MANE Select	c.*1911G>C		3_prime_UTR	Exon 5 of 5	ENSP00000242728.4

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74711 AN: 151928 Hom.: 20964 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.606 AC: 154 AN: 254 Hom.: 45 Cov.: 0 AF XY: 0.623 AC XY: 96 AN XY: 154

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.612 AC: 153 AN: 250

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.491 AC: 74726 AN: 152048 Hom.: 20966 Cov.: 33 AF XY: 0.494 AC XY: 36691 AN XY: 74322

African (AFR) AF: 0.200 AC: 8289 AN: 41494

American (AMR) AF: 0.612 AC: 9365 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1982 AN: 3468

East Asian (EAS) AF: 0.779 AC: 4027 AN: 5170

South Asian (SAS) AF: 0.509 AC: 2448 AN: 4810

European-Finnish (FIN) AF: 0.615 AC: 6469 AN: 10520

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.592 AC: 40221 AN: 67976

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.534 Hom.: 2851

Bravo AF: 0.484

Asia WGS AF: 0.613 AC: 2129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.21
DANN	Benign	0.71
PhyloP100		-0.058
Mutation Taster		=100/0	polymorphism (auto)

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: rs1048155; hg19: chr12-26273088;