Variant rs1056663 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004507.4(HUS1):c.834G>A(p.Ala278Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,605,974 control chromosomes in the GnomAD database, including 203,921 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 0.46 ( 16801 hom., cov: 33)

Exomes 𝑓: 0.50 ( 187120 hom. )

Consequence

HUS1
NM_004507.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.24

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:

HUS1 (HGNC:):

HUS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP7

Synonymous conserved (PhyloP=-2.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HUS1	NM_004507.4 linkuse as main transcript	c.834G>A	p.Ala278Ala	synonymous_variant	8/8	ENST00000258774.10	NP_004498.1	O60921-1A4D2F2
HUS1	NM_001363683.2 linkuse as main transcript	c.771G>A	p.Ala257Ala	synonymous_variant	8/8		NP_001350612.1
HUS1	NR_037917.2 linkuse as main transcript	n.988G>A		non_coding_transcript_exon_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HUS1	ENST00000258774.10 linkuse as main transcript	c.834G>A	p.Ala278Ala	synonymous_variant	8/8	1	NM_004507.4	ENSP00000258774.5	O60921-1
HUS1	ENST00000432325.5 linkuse as main transcript	c.771G>A	p.Ala257Ala	synonymous_variant	8/8	5		ENSP00000416588.1	O60921-2
HUS1	ENST00000458191.5 linkuse as main transcript	n.771G>A		non_coding_transcript_exon_variant	8/9	2		ENSP00000400727.1	O60921-2

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69868

AN:

151892

Hom.:

16804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.537

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.590

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.451

GnomAD3 exomes

AF:

0.491

AC:

123259

AN:

251266

Hom.:

31054

AF XY:

0.485

AC XY:

65905

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.522

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.549

Gnomad SAS exome

AF:

0.381

Gnomad FIN exome

AF:

0.586

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.485

GnomAD4 exome

AF:

0.504

AC:

732621

AN:

1453964

Hom.:

187120

Cov.:

AF XY:

0.500

AC XY:

362118

AN XY:

723714

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.520

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.526

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.583

Gnomad4 NFE exome

AF:

0.517

Gnomad4 OTH exome

AF:

0.487

GnomAD4 genome

AF:

0.460

AC:

69884

AN:

152010

Hom.:

16801

Cov.:

AF XY:

0.465

AC XY:

34535

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.450

Gnomad4 EAS

AF:

0.537

Gnomad4 SAS

AF:

0.388

Gnomad4 FIN

AF:

0.590

Gnomad4 NFE

AF:

0.520

Gnomad4 OTH

AF:

0.448

Alfa

AF:

0.490

Hom.:

11621

Bravo

AF:

0.446

Asia WGS

AF:

0.477

AC:

1659

AN:

3478

EpiCase

AF:

0.505

EpiControl

AF:

0.495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.30

DANN

Benign

0.47

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over