17-2056942-C-A

Variant names:

• chr17-2056942-C-A
• rs766201575
• NM_006497.4:c.252C>A

Variant summary

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

The NM_006497.4(HIC1):​c.252C>A​(p.Thr84Thr) 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. Synonymous variant affecting the same amino acid position (i.e. T84T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: HIC1 NM_006497.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 0 publications found

Genes affected

HIC1 (HGNC:4909): (HIC ZBTB transcriptional repressor 1) This gene functions as a growth regulatory and tumor repressor gene. Hypermethylation or deletion of the region of this gene have been associated with tumors and the contiguous-gene syndrome, Miller-Dieker syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2010]

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=-0.28).
• BP7: Synonymous conserved (PhyloP=-0.95 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006497.4. 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
	HIC1	NM_006497.4	MANE Select	c.252C>A	p.Thr84Thr	synonymous	Exon 2 of 2	NP_006488.2	Q14526-2
	HIC1	NM_001098202.1		c.309C>A	p.Thr103Thr	synonymous	Exon 2 of 2	NP_001091672.1	Q14526-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIC1	ENST00000619757.5	TSL:1 MANE Select	c.252C>A	p.Thr84Thr	synonymous	Exon 2 of 2	ENSP00000477858.1	Q14526-2
	HIC1	ENST00000399849.4	TSL:1	c.252C>A	p.Thr84Thr	synonymous	Exon 2 of 2	ENSP00000382742.2	Q14526-2
	HIC1	ENST00000571990.1	TSL:1	c.252C>A	p.Thr84Thr	synonymous	Exon 3 of 3	ENSP00000460268.1	I3L388

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		-0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766201575; hg19: chr17-1960236;