Genetic Variant HUS1:c.53-264A>G (chr7-47979080-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004507.4(HUS1):c.53-264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 152,174 control chromosomes in the GnomAD database, including 334 homozygotes. 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: 𝑓 0.046 ( 334 hom., cov: 32)

Consequence

HUS1
NM_004507.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.90

Publications

3 publications found

Variant links:

Genes affected

HUS1 (HGNC:5309): (HUS1 checkpoint clamp component) The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. This protein forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1. In response to DNA damage, the trimeric complex interacts with another protein complex consisting of checkpoint protein RAD17 and four small subunits of the replication factor C (RFC), which loads the combined complex onto the chromatin. The DNA damage induced chromatin binding has been shown to depend on the activation of the checkpoint kinase ATM, and is thought to be an early checkpoint signaling event. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]

HUS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HUS1	NM_004507.4	MANE Select	c.53-264A>G	intron	N/A	NP_004498.1	A4D2F2
HUS1	NM_001363683.2		c.-11-264A>G	intron	N/A	NP_001350612.1	O60921-2
HUS1	NR_037917.2		n.207-264A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HUS1	ENST00000258774.10	TSL:1 MANE Select	c.53-264A>G	intron	N/A	ENSP00000258774.5	O60921-1
HUS1	ENST00000857245.1		c.53-264A>G	intron	N/A	ENSP00000527304.1
HUS1	ENST00000921487.1		c.53-264A>G	intron	N/A	ENSP00000591546.1

Frequencies

GnomAD3 genomes

AF:

0.0462

AC:

7019

AN:

152056

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.0975

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0467

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00801

Gnomad OTH

AF:

0.0369

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0462

AC:

7027

AN:

152174

Hom.:

334

Cov.:

AF XY:

0.0473

AC XY:

3518

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.118

AC:

4913

AN:

41486

American (AMR)

AF:

0.0202

AC:

309

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.0974

AC:

503

AN:

5166

South Asian (SAS)

AF:

0.0205

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0467

AC:

495

AN:

10598

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00801

AC:

545

AN:

68012

Other (OTH)

AF:

0.0365

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

311

623

934

1246

1557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0192

Hom.:

122

Bravo

AF:

0.0489

Asia WGS

AF:

0.0590

AC:

203

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.53

(source)

DANN

Benign

0.42

PhyloP100

-3.9

PromoterAI

0.041

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over