rs3088180

Positions:

• chr2-75702112-C-A
• chr2-75702112-C-G

Variant summary

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

The ENST00000470503.1(GCFC2):​c.*58G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,517,722 control chromosomes in the GnomAD database, including 139,030 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 0.50 (20462 hom., cov: 32)
  • Exomes 𝑓: 0.41 (118568 hom.)
• Consequence: GCFC2 ENST00000470503.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCFC2	NM_003203.5	c.619+87G>T		intron_variant		ENST00000321027.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCFC2	ENST00000321027.8	c.619+87G>T		intron_variant		1	NM_003203.5	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75742 AN: 151856 Hom.: 20425 Cov.: 32

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.412 AC: 562138 AN: 1365748 Hom.: 118568 Cov.: 23 AF XY: 0.409 AC XY: 277144 AN XY: 676910

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.347

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.457

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.499 AC: 75830 AN: 151974 Hom.: 20462 Cov.: 32 AF XY: 0.497 AC XY: 36907 AN XY: 74268

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.424

Alfa AF: 0.491 Hom.: 3501

Bravo AF: 0.508

Asia WGS AF: 0.422 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.80
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3088180; hg19: chr2-75929238; COSMIC: COSV58081260; COSMIC: COSV58081260;