rs2037483

Positions:

• chr7-47965525-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000258774.10(HUS1):​c.761-87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 867,144 control chromosomes in the GnomAD database, including 104,727 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 (16791 hom., cov: 33)
  • Exomes 𝑓: 0.49 (87936 hom.)
• Consequence: HUS1 ENST00000258774.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HUS1	NM_004507.4	c.761-87C>T		intron_variant		ENST00000258774.10	NP_004498.1
HUS1	NM_001363683.2	c.698-87C>T		intron_variant			NP_001350612.1
HUS1	NR_037917.2	n.915-87C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HUS1	ENST00000258774.10	c.761-87C>T		intron_variant		1	NM_004507.4	ENSP00000258774	P1
HUS1	ENST00000432325.5	c.698-87C>T		intron_variant		5		ENSP00000416588
HUS1	ENST00000458191.5	c.698-87C>T		intron_variant, NMD_transcript_variant		2		ENSP00000400727

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69860 AN: 151910 Hom.: 16794 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.450

GnomAD4 exome AF: 0.490 AC: 350325 AN: 715116 Hom.: 87936 AF XY: 0.485 AC XY: 183038 AN XY: 377248

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.519

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.578

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.460 AC: 69875 AN: 152028 Hom.: 16791 Cov.: 33 AF XY: 0.465 AC XY: 34531 AN XY: 74314

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.447

Alfa AF: 0.497 Hom.: 2558

Bravo AF: 0.446

Asia WGS AF: 0.476 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs2037483; hg19: chr7-48005122; COSMIC: COSV51840334; COSMIC: COSV51840334;