rs2291778

Variant names:

• chr17-750578-G-T
• rs2291778
• NM_015721.3:c.10+1555C>A

Variant summary

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

The NM_015721.3(GEMIN4):​c.10+1555C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,148 control chromosomes in the GnomAD database, including 1,003 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 0.10 (1003 hom., cov: 32)
• Consequence: GEMIN4 NM_015721.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 22 publications found

Genes affected

GEMIN4 (HGNC:15717): (gem nuclear organelle associated protein 4) The product of this gene is part of a large complex localized to the cytoplasm, nucleoli, and to discrete nuclear bodies called Gemini bodies (gems). The complex functions in spliceosomal snRNP assembly in the cytoplasm, and regenerates spliceosomes required for pre-mRNA splicing in the nucleus. The encoded protein directly interacts with a DEAD box protein and several spliceosome core proteins. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

GEMIN4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN4	NM_015721.3	c.10+1555C>A		intron_variant	Intron 1 of 1	ENST00000319004.6	NP_056536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN4	ENST00000319004.6	c.10+1555C>A		intron_variant	Intron 1 of 1	1	NM_015721.3	ENSP00000321706.5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15858 AN: 152030 Hom.: 1005 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.104 AC: 15857 AN: 152148 Hom.: 1003 Cov.: 32 AF XY: 0.108 AC XY: 8043 AN XY: 74386

African (AFR) AF: 0.0525 AC: 2178 AN: 41520

American (AMR) AF: 0.144 AC: 2206 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1207 AN: 5164

South Asian (SAS) AF: 0.0488 AC: 235 AN: 4814

European-Finnish (FIN) AF: 0.200 AC: 2120 AN: 10590

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.103 AC: 6976 AN: 67996

Other (OTH) AF: 0.111 AC: 235 AN: 2110

Alfa AF: 0.108 Hom.: 4089

Bravo AF: 0.105

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.41
PhyloP100		-0.24
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: rs2291778; hg19: chr17-653818; COSMIC: COSV59791232; COSMIC: COSV59791232;