rs761025

Positions:

• chr20-25446332-G-A
• chr20-25446332-G-C

Variant summary

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

The NM_021067.5(GINS1):​c.*341G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 206,286 control chromosomes in the GnomAD database, including 21,707 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 0.43 (14910 hom., cov: 32)
  • Exomes 𝑓: 0.47 (6797 hom.)
• Consequence: GINS1 NM_021067.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GINS1	NM_021067.5	c.*341G>A		3_prime_UTR_variant	7/7	ENST00000262460.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GINS1	ENST00000262460.5	c.*341G>A		3_prime_UTR_variant	7/7	1	NM_021067.5	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65553 AN: 151442 Hom.: 14906 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.474 AC: 25961 AN: 54728 Hom.: 6797 Cov.: 0 AF XY: 0.475 AC XY: 13111 AN XY: 27602

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.917

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.433 AC: 65583 AN: 151558 Hom.: 14910 Cov.: 32 AF XY: 0.435 AC XY: 32207 AN XY: 74124

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.410

Alfa AF: 0.430 Hom.: 3554

Bravo AF: 0.425

Asia WGS AF: 0.676 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.58

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: rs761025; hg19: chr20-25426968;