rs4853169

Positions:

• chr2-75679846-G-A
• chr2-75679846-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003203.5(GCFC2):​c.1812+347C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 406,642 control chromosomes in the GnomAD database, including 10,620 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 0.19 (3481 hom., cov: 33)
  • Exomes 𝑓: 0.23 (7139 hom.)
• Consequence: GCFC2 NM_003203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

Genes affected

GCFC2 (HGNC:1317): (GC-rich sequence DNA-binding factor 2) The first mRNA transcript isolated for this gene was part of an artificial chimera derived from two distinct gene transcripts and a primer used in the cloning process (see Genbank accession M29204). A positively charged amino terminus present only in the chimera was determined to bind GC-rich DNA, thus mistakenly thought to identify a transcription factor gene. [provided by RefSeq, Jul 2008]

LOC124906025 (HGNC:):

MRPL19 (HGNC:14052): (mitochondrial ribosomal protein L19) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCFC2	NM_003203.5	c.1812+347C>T		intron_variant		ENST00000321027.8
LOC124906025	XR_007087113.1	n.7531G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCFC2	ENST00000321027.8	c.1812+347C>T		intron_variant		1	NM_003203.5	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29129 AN: 152014 Hom.: 3476 Cov.: 33

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.182

GnomAD3 exomes AF: 0.193 AC: 280 AN: 1450 Hom.: 32 AF XY: 0.194 AC XY: 154 AN XY: 792

Gnomad AFR exome AF: 0.0667

Gnomad AMR exome AF: 0.268

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.226

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.238

GnomAD4 exome AF: 0.229 AC: 58265 AN: 254510 Hom.: 7139 Cov.: 0 AF XY: 0.230 AC XY: 29679 AN XY: 129174

Gnomad4 AFR exome AF: 0.0565

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.192 AC: 29143 AN: 152132 Hom.: 3481 Cov.: 33 AF XY: 0.193 AC XY: 14362 AN XY: 74356

Gnomad4 AFR AF: 0.0532

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.181

Alfa AF: 0.240 Hom.: 2383

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.7
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs4853169; hg19: chr2-75906972; COSMIC: COSV58082482;