rs761025

Variant names:

• chr20-25446332-G-A
• rs761025
• NM_021067.5:c.*341G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-25446332-G-A
• chr20-25446332-G-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.*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
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS1	NM_021067.5	MANE Select	c.*341G>A		3_prime_UTR	Exon 7 of 7	NP_066545.3
	GINS1	NM_001410830.1		c.*341G>A		3_prime_UTR	Exon 6 of 6	NP_001397759.1	A0A8Q3WLL7
	GINS1	NM_001410831.1		c.*341G>A		3_prime_UTR	Exon 4 of 4	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.*341G>A		3_prime_UTR	Exon 7 of 7	ENSP00000262460.4	Q14691
	GINS1	ENST00000696814.1		c.*453G>A		3_prime_UTR	Exon 8 of 8	ENSP00000512895.1	A0A8Q3WMM5
	GINS1	ENST00000696806.1		c.*341G>A		3_prime_UTR	Exon 4 of 4	ENSP00000512885.1	A0A8Q3WLJ3

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

African (AFR) AF: 0.386 AC: 826 AN: 2138

American (AMR) AF: 0.344 AC: 635 AN: 1846

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 813 AN: 2530

East Asian (EAS) AF: 0.917 AC: 4236 AN: 4618

South Asian (SAS) AF: 0.476 AC: 362 AN: 760

European-Finnish (FIN) AF: 0.468 AC: 1311 AN: 2800

Middle Eastern (MID) AF: 0.319 AC: 86 AN: 270

European-Non Finnish (NFE) AF: 0.444 AC: 15886 AN: 35764

Other (OTH) AF: 0.451 AC: 1806 AN: 4002

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

African (AFR) AF: 0.379 AC: 15525 AN: 41016

American (AMR) AF: 0.376 AC: 5746 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3470

East Asian (EAS) AF: 0.918 AC: 4755 AN: 5182

South Asian (SAS) AF: 0.473 AC: 2278 AN: 4812

European-Finnish (FIN) AF: 0.451 AC: 4768 AN: 10570

Middle Eastern (MID) AF: 0.400 AC: 116 AN: 290

European-Non Finnish (NFE) AF: 0.441 AC: 29968 AN: 67938

Other (OTH) AF: 0.410 AC: 863 AN: 2106

Alfa AF: 0.428 Hom.: 5545

Bravo AF: 0.425

Asia WGS AF: 0.676 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-1.4
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: rs761025; hg19: chr20-25426968;