7-47979080-T-C

Position:

• chr7-47979080-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.90

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HUS1	NM_004507.4	c.53-264A>G		intron_variant		ENST00000258774.10	NP_004498.1
HUS1	NM_001363683.2	c.-11-264A>G		intron_variant			NP_001350612.1
HUS1	NR_037917.2	n.207-264A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HUS1	ENST00000258774.10	c.53-264A>G		intron_variant		1	NM_004507.4	ENSP00000258774	P1

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7019 AN: 152056 Hom.: 334 Cov.: 32

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.: 32 AF XY: 0.0473 AC XY: 3518 AN XY: 74410

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.0974

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0467

Gnomad4 NFE AF: 0.00801

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0148 Hom.: 56

Bravo AF: 0.0489

Asia WGS AF: 0.0590 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.53
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs3176499; hg19: chr7-48018677;