rs2037483

Variant names:

• chr7-47965525-G-A
• rs2037483
• NM_004507.4:c.761-87C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-47965525-G-A
• chr7-47965525-G-T

Variant summary

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

The NM_004507.4(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 NM_004507.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 8 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=-0.87).
• 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 rank	MANE	Protein	UniProt
HUS1	NM_004507.4	c.761-87C>T		intron_variant	Intron 7 of 7	ENST00000258774.10	NP_004498.1
HUS1	NM_001363683.2	c.698-87C>T		intron_variant	Intron 7 of 7		NP_001350612.1
HUS1	NR_037917.2	n.915-87C>T		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HUS1	ENST00000258774.10	c.761-87C>T		intron_variant	Intron 7 of 7	1	NM_004507.4	ENSP00000258774.5
HUS1	ENST00000432325.6	c.698-87C>T		intron_variant	Intron 7 of 7	5		ENSP00000416588.1
HUS1	ENST00000458191.5	n.698-87C>T		intron_variant	Intron 7 of 8	2		ENSP00000400727.1

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

African (AFR) AF: 0.305 AC: 5832 AN: 19150

American (AMR) AF: 0.512 AC: 18274 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 8749 AN: 19366

East Asian (EAS) AF: 0.519 AC: 16949 AN: 32664

South Asian (SAS) AF: 0.379 AC: 24206 AN: 63858

European-Finnish (FIN) AF: 0.578 AC: 24063 AN: 41630

Middle Eastern (MID) AF: 0.399 AC: 1723 AN: 4318

European-Non Finnish (NFE) AF: 0.504 AC: 233545 AN: 463104

Other (OTH) AF: 0.480 AC: 16984 AN: 35358

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

African (AFR) AF: 0.314 AC: 13038 AN: 41458

American (AMR) AF: 0.497 AC: 7589 AN: 15282

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

East Asian (EAS) AF: 0.536 AC: 2759 AN: 5152

South Asian (SAS) AF: 0.388 AC: 1871 AN: 4828

European-Finnish (FIN) AF: 0.591 AC: 6240 AN: 10562

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.520 AC: 35324 AN: 67960

Other (OTH) AF: 0.447 AC: 945 AN: 2112

Alfa AF: 0.493 Hom.: 27703

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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