rs2500406

chr20-25421226-A-C

Variant summary

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

The NM_021067.5(GINS1):c.330+3031A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,108 control chromosomes in the GnomAD database, including 37,621 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 0.69 (37621 hom., cov: 33)
• Consequence: GINS1 NM_021067.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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 (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GINS1	NM_021067.5	c.330+3031A>C		intron_variant		ENST00000262460.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GINS1	ENST00000262460.5	c.330+3031A>C		intron_variant		1	NM_021067.5	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105028 AN: 151990 Hom.: 37572 Cov.: 33

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.691 AC: 105140 AN: 152108 Hom.: 37621 Cov.: 33 AF XY: 0.687 AC XY: 51068 AN XY: 74354

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.693

Alfa AF: 0.682 Hom.: 23162

Bravo AF: 0.695

Asia WGS AF: 0.395 AC: 1378 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	2.8
Dann	Benign	0.67

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: rs2500406; hg19: chr20-25401862;