rs6050598

Variant names:

• chr20-25416621-G-C
• rs6050598
• NM_021067.5:c.141-483G>C

Variant summary

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

The NM_021067.5(GINS1):​c.141-483G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,038 control chromosomes in the GnomAD database, including 22,824 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 0.54 (22824 hom., cov: 32)
• Consequence: GINS1 NM_021067.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 12 publications found

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]

GINS1 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to GINS1 deficiency

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021067.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS1	NM_021067.5	MANE Select	c.141-483G>C		intron	N/A	NP_066545.3
	GINS1	NM_001410830.1		c.141-483G>C		intron	N/A	NP_001397759.1
	GINS1	NM_001410831.1		c.76-8590G>C		intron	N/A	NP_001397760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS1	ENST00000262460.5	TSL:1 MANE Select	c.141-483G>C		intron	N/A	ENSP00000262460.4
	GINS1	ENST00000696814.1		c.141-483G>C		intron	N/A	ENSP00000512895.1
	GINS1	ENST00000696894.1		c.141-483G>C		intron	N/A	ENSP00000512956.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82154 AN: 151920 Hom.: 22798 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.541 AC: 82230 AN: 152038 Hom.: 22824 Cov.: 32 AF XY: 0.540 AC XY: 40118 AN XY: 74318

African (AFR) AF: 0.538 AC: 22311 AN: 41458

American (AMR) AF: 0.609 AC: 9308 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2358 AN: 3468

East Asian (EAS) AF: 0.0824 AC: 426 AN: 5172

South Asian (SAS) AF: 0.523 AC: 2518 AN: 4818

European-Finnish (FIN) AF: 0.548 AC: 5790 AN: 10564

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37721 AN: 67966

Other (OTH) AF: 0.562 AC: 1189 AN: 2114

Alfa AF: 0.547 Hom.: 2847

Bravo AF: 0.544

Asia WGS AF: 0.318 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.43
DANN	Benign	0.58
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6050598; hg19: chr20-25397257;