chr17-2056800-C-T

Variant names:

• chr17-2056800-C-T
• rs200866682
• NM_006497.4:c.110C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006497.4(HIC1):​c.110C>T​(p.Ala37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000893 in 1,612,802 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A37S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000090 (5 hom.)
• Consequence: HIC1 NM_006497.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39
• Publications: 4 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10927221).
• BS2: High AC in GnomAd4 at 12 AD gene.

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.110C>T	p.Ala37Val	missense	Exon 2 of 2	NP_006488.2	Q14526-2
	HIC1	NM_001098202.1		c.167C>T	p.Ala56Val	missense	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.110C>T	p.Ala37Val	missense	Exon 2 of 2	ENSP00000477858.1	Q14526-2
	HIC1	ENST00000399849.4	TSL:1	c.110C>T	p.Ala37Val	missense	Exon 2 of 2	ENSP00000382742.2	Q14526-2
	HIC1	ENST00000571990.1	TSL:1	c.110C>T	p.Ala37Val	missense	Exon 3 of 3	ENSP00000460268.1	I3L388

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152236 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000126 AC: 31 AN: 246536 AF XY: 0.000171

Gnomad AFR exome AF: 0.0000655

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000451

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000904 AC: 132 AN: 1460448 Hom.: 5 Cov.: 32 AF XY: 0.000124 AC XY: 90 AN XY: 726508

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.000927 AC: 80 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1111830

Other (OTH) AF: 0.000199 AC: 12 AN: 60364

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152354 Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 9 AN XY: 74516

African (AFR) AF: 0.0000240 AC: 1 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000310 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.000149 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.65	N
PhyloP100		2.4
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.36
Sift	Benign	0.12	T
Sift4G	Benign	0.68	T
Polyphen		1.0	D
Vest4		0.58
MVP		0.57
ClinPred		0.12	T
GERP RS		4.1
PromoterAI		0.019	Neutral
Varity_R		0.30
gMVP		0.65
Mutation Taster		=71/29	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: rs200866682; hg19: chr17-1960094;