1-999365-C-T

Variant names:

• chr1-999365-C-T
• rs567970457
• NM_021170.4:c.360G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_021170.4(HES4):​c.360G>A​(p.Glu120Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HES4 NM_021170.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804
• Publications: 0 publications found

Genes affected

HES4 (HGNC:24149): (hes family bHLH transcription factor 4) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anterior/posterior pattern specification and regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.804 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021170.4. 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
	HES4	NM_021170.4	MANE Select	c.360G>A	p.Glu120Glu	synonymous	Exon 4 of 4	NP_066993.1	Q9HCC6
	HES4	NM_001142467.2		c.438G>A	p.Glu146Glu	synonymous	Exon 3 of 3	NP_001135939.1	E9PB28
	HES4	NM_001410700.1		c.264G>A	p.Glu88Glu	synonymous	Exon 3 of 3	NP_001397629.1	D6REB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HES4	ENST00000304952.11	TSL:1 MANE Select	c.360G>A	p.Glu120Glu	synonymous	Exon 4 of 4	ENSP00000304595.7	Q9HCC6
	HES4	ENST00000428771.6	TSL:2	c.438G>A	p.Glu146Glu	synonymous	Exon 3 of 3	ENSP00000393198.2	E9PB28
	HES4	ENST00000854802.1		c.300G>A	p.Glu100Glu	synonymous	Exon 4 of 4	ENSP00000524863.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1346164 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 665196

African (AFR) AF: 0.00 AC: 0 AN: 27904

American (AMR) AF: 0.00 AC: 0 AN: 26906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22912

East Asian (EAS) AF: 0.00 AC: 0 AN: 31568

South Asian (SAS) AF: 0.00 AC: 0 AN: 73936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067316

Other (OTH) AF: 0.00 AC: 0 AN: 55934

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.80
Mutation Taster		=97/3	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: rs567970457; hg19: chr1-934745;