7-47977120-T-G

Variant names:

• chr7-47977120-T-G
• rs2708861
• NM_004507.4:c.358-283A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004507.4(HUS1):​c.358-283A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,850 control chromosomes in the GnomAD database, including 16,811 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 (16811 hom., cov: 31)
• Consequence: HUS1 NM_004507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 11 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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 rank	MANE	Protein	UniProt
HUS1	NM_004507.4	c.358-283A>C		intron_variant	Intron 3 of 7	ENST00000258774.10	NP_004498.1
HUS1	NM_001363683.2	c.295-283A>C		intron_variant	Intron 3 of 7		NP_001350612.1
HUS1	NR_037917.2	n.512-283A>C		intron_variant	Intron 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HUS1	ENST00000258774.10	c.358-283A>C		intron_variant	Intron 3 of 7	1	NM_004507.4	ENSP00000258774.5

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69835 AN: 151732 Hom.: 16814 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.460 AC: 69851 AN: 151850 Hom.: 16811 Cov.: 31 AF XY: 0.465 AC XY: 34498 AN XY: 74188

African (AFR) AF: 0.314 AC: 13011 AN: 41384

American (AMR) AF: 0.497 AC: 7588 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1564 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2771 AN: 5160

South Asian (SAS) AF: 0.388 AC: 1861 AN: 4798

European-Finnish (FIN) AF: 0.591 AC: 6206 AN: 10506

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.520 AC: 35360 AN: 67952

Other (OTH) AF: 0.447 AC: 944 AN: 2110

Alfa AF: 0.497 Hom.: 70220

Bravo AF: 0.446

Asia WGS AF: 0.478 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.062
DANN	Benign	0.50
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2708861; hg19: chr7-48016717;