chr20-25407901-G-A

Variant names:

• chr20-25407901-G-A
• rs2090256889
• NM_021067.5:c.75+6G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021067.5(GINS1):​c.75+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GINS1 NM_021067.5 splice_region, intron
• Scores: Splicing: ADA: 0.0004056
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.673
• Publications: 0 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

LOC105372581 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS1	NM_021067.5	MANE Select	c.75+6G>A		splice_region intron	N/A	NP_066545.3
	GINS1	NM_001410830.1		c.75+6G>A		splice_region intron	N/A	NP_001397759.1	A0A8Q3WLL7
	GINS1	NM_001410831.1		c.75+6G>A		splice_region intron	N/A	NP_001397760.1	A0A8Q3WLJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS1	ENST00000262460.5	TSL:1 MANE Select	c.75+6G>A		splice_region intron	N/A	ENSP00000262460.4	Q14691
	GINS1	ENST00000696814.1		c.75+6G>A		splice_region intron	N/A	ENSP00000512895.1	A0A8Q3WMM5
	GINS1	ENST00000696894.1		c.75+6G>A		splice_region intron	N/A	ENSP00000512956.1	A0A8Q3SJ10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.3
DANN	Benign	0.90
PhyloP100		-0.67
PromoterAI		0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00041
dbscSNV1_RF	Benign	0.028
SpliceAI score (max)		0.65		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.65		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2090256889; hg19: chr20-25388537;