Variant 4-3074876-CCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-CCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BA1

The NM_001388492.1(HTT):c.105_110delGCAGCA(p.Gln36_Gln37del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.245 in 1,348,998 control chromosomes in the GnomAD database, including 35,626 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.20 ( 3269 hom., cov: 0)

Exomes 𝑓: 0.25 ( 32357 hom. )

Consequence

HTT
NM_001388492.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 5.65

Variant links:

Genes affected

HTT (HGNC:4851): (huntingtin) Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range of trinucleotide repeats (9-35) has been identified in normal controls, and repeat numbers in excess of 40 have been described as pathological. The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. The huntingtin gene is widely expressed and is required for normal development. It is expressed as 2 alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues. The larger transcript is approximately 13.7 kb and is expressed predominantly in adult and fetal brain whereas the smaller transcript of approximately 10.3 kb is more widely expressed. The genetic defect leading to Huntington's disease may not necessarily eliminate transcription, but may confer a new property on the mRNA or alter the function of the protein. One candidate is the huntingtin-associated protein-1, highly expressed in brain, which has increased affinity for huntingtin protein with expanded polyglutamine repeats. This gene contains an upstream open reading frame in the 5' UTR that inhibits expression of the huntingtin gene product through translational repression. [provided by RefSeq, Jul 2016]

HTT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001388492.1

BP6

Variant 4-3074876-CCAGCAG-C is Benign according to our data. Variant chr4-3074876-CCAGCAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 1328024.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTT	NM_001388492.1 link	c.105_110delGCAGCA	p.Gln36_Gln37del	disruptive_inframe_deletion	1/67	ENST00000355072.11	NP_001375421.1
HTT	NM_002111.8 link	c.105_110delGCAGCA	p.Gln36_Gln37del	disruptive_inframe_deletion	1/67		NP_002102.4	P42858

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTT	ENST00000355072.11 link	c.105_110delGCAGCA	p.Gln36_Gln37del	disruptive_inframe_deletion	1/67	1	NM_001388492.1	ENSP00000347184.5		P42858

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

26654

AN:

131118

Hom.:

3269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.384

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.225

GnomAD4 exome

AF:

0.249

AC:

303610

AN:

1217784

Hom.:

32357

AF XY:

0.252

AC XY:

152292

AN XY:

603946

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.212

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.364

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.203

AC:

26660

AN:

131214

Hom.:

3269

Cov.:

AF XY:

0.206

AC XY:

13028

AN XY:

63102

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.315

Gnomad4 SAS

AF:

0.413

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.223

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over