NM_021067.5:c.330+3031A>C

Variant names:

• chr20-25421226-A-C
• rs2500406
• NM_021067.5:c.330+3031A>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.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
• Publications: 18 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=-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 rank	MANE	Protein	UniProt
GINS1	NM_021067.5	c.330+3031A>C		intron_variant	Intron 4 of 6	ENST00000262460.5	NP_066545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GINS1	ENST00000262460.5	c.330+3031A>C		intron_variant	Intron 4 of 6	1	NM_021067.5	ENSP00000262460.4

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

African (AFR) AF: 0.808 AC: 33501 AN: 41472

American (AMR) AF: 0.696 AC: 10638 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2638 AN: 3468

East Asian (EAS) AF: 0.0859 AC: 445 AN: 5180

South Asian (SAS) AF: 0.647 AC: 3115 AN: 4818

European-Finnish (FIN) AF: 0.684 AC: 7228 AN: 10574

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45397 AN: 67992

Other (OTH) AF: 0.693 AC: 1464 AN: 2114

Alfa AF: 0.699 Hom.: 38270

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
PhyloP100		-0.64
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: rs2500406; hg19: chr20-25401862;