dbSNP rs10597644: HIC2:c.*525_*528delTCAG (chr22-21447264-ACAGT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_015094.3(HIC2):c.*525_*528delTCAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 158,110 control chromosomes in the GnomAD database, including 54 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 54 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

HIC2
NM_015094.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

0 publications found

Variant links:

Genes affected

HIC2 (HGNC:18595): (HIC ZBTB transcriptional repressor 2) Enables protein C-terminus binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

HIC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2142/152308) while in subpopulation AFR AF = 0.0485 (2017/41554). AF 95% confidence interval is 0.0468. There are 54 homozygotes in GnomAd4. There are 1025 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2142 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015094.3. 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
	HIC2	NM_015094.3	MANE Select	c.525_528delTCAG		3_prime_UTR	Exon 3 of 3	NP_055909.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HIC2	ENST00000407464.7	TSL:1 MANE Select	c.525_528delTCAG	3_prime_UTR	Exon 3 of 3	ENSP00000385319.2
HIC2	ENST00000407598.2	TSL:1	c.525_528delTCAG	3_prime_UTR	Exon 3 of 3	ENSP00000384889.2
HIC2	ENST00000443632.2	TSL:1	c.525_528delTCAG	3_prime_UTR	Exon 2 of 2	ENSP00000387757.2

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2129

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00121

AC:

AN:

5802

Hom.:

AF XY:

0.00166

AC XY:

AN XY:

3010

show subpopulations

African (AFR)

AF:

0.0750

AC:

AN:

American (AMR)

AF:

0.00105

AC:

AN:

952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

112

East Asian (EAS)

AF:

0.00

AC:

AN:

210

South Asian (SAS)

AF:

0.00

AC:

AN:

280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

3456

Other (OTH)

AF:

0.00

AC:

AN:

220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0141

AC:

2142

AN:

152308

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1025

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0485

AC:

2017

AN:

41554

American (AMR)

AF:

0.00601

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68028

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

102

204

307

409

511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.0161

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over