rs6050626

Positions:

• chr20-25447625-T-C

Variant summary

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

The NM_021067.5(GINS1):​c.*1634T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,044 control chromosomes in the GnomAD database, including 16,616 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 (16615 hom., cov: 33)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: GINS1 NM_021067.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764

Genes affected

GINS1 (HGNC:28980): (GINS complex subunit 1) The yeast heterotetrameric GINS complex is made up of Sld5 (GINS4; MIM 610611), Psf1, Psf2 (GINS2; MIM 610609), and Psf3 (GINS3; MIM 610610). The formation of the GINS complex is essential for the initiation of DNA replication in yeast and Xenopus egg extracts (Ueno et al., 2005 [PubMed 16287864]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GINS1	NM_021067.5	c.*1634T>C		3_prime_UTR_variant	7/7	ENST00000262460.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GINS1	ENST00000262460.5	c.*1634T>C		3_prime_UTR_variant	7/7	1	NM_021067.5	P1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69792 AN: 151922 Hom.: 16605 Cov.: 33

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.459 AC: 69835 AN: 152040 Hom.: 16615 Cov.: 33 AF XY: 0.460 AC XY: 34193 AN XY: 74318

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.438

Alfa AF: 0.433 Hom.: 14139

Bravo AF: 0.456

Asia WGS AF: 0.682 AC: 2369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6050626; hg19: chr20-25428261; COSMIC: COSV52466062;