1-2529928-C-T

Variant names:

• chr1-2529928-C-T
• rs778489792
• NM_001010926.4:c.138G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001010926.4(HES5):​c.138G>A​(p.Glu46Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,455,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: HES5 NM_001010926.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

Genes affected

HES5 (HGNC:19764): (hes family bHLH transcription factor 5) This gene encodes a member of a family of basic helix-loop-helix transcriptional repressors. The protein product of this gene, which is activated downstream of the Notch pathway, regulates cell differentiation in multiple tissues. Disruptions in the normal expression of this gene have been associated with developmental diseases and cancer. [provided by RefSeq, Dec 2008]

ENSG00000272449 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=1.83 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010926.4. 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
	HES5	NM_001010926.4	MANE Select	c.138G>A	p.Glu46Glu	synonymous	Exon 2 of 3	NP_001010926.1	Q5TA89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HES5	ENST00000378453.4	TSL:1 MANE Select	c.138G>A	p.Glu46Glu	synonymous	Exon 2 of 3	ENSP00000367714.3	Q5TA89
	ENSG00000272449	ENST00000644246.1		n.-136C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1455844 Hom.: 0 Cov.: 33 AF XY: 0.00000553 AC XY: 4 AN XY: 723936

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.00 AC: 0 AN: 85312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1109740

Other (OTH) AF: 0.00 AC: 0 AN: 60112

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		1.8
PromoterAI		0.0039	Neutral
Mutation Taster		=98/2	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: rs778489792; hg19: chr1-2461367;