rs2412522

Positions:

• chr4-54072376-A-G

Variant summary

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

The ENST00000507166.5(ENSG00000282278):​c.1018-202549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,944 control chromosomes in the GnomAD database, including 6,152 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 0.28 (6152 hom., cov: 31)
• Consequence: ENSG00000282278 ENST00000507166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

Genes affected

ENSG00000282278 (HGNC:):

CHIC2 (HGNC:1935): (cysteine rich hydrophobic domain 2) This gene encodes a member of the CHIC family of proteins. The encoded protein contains a cysteine-rich hydrophobic (CHIC) motif, and is localized to vesicular structures and the plasma membrane. This gene is associated with some cases of acute myeloid leukemia. [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 (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHIC2	XM_047450063.1	c.-1493-5569T>C		intron_variant			XP_047306019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000282278	ENST00000507166.5	c.1018-202549A>G		intron_variant		2		ENSP00000423325.1
ENSG00000287534	ENST00000654316.1	n.1611-4864A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42465 AN: 151826 Hom.: 6145 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.0879

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.280 AC: 42506 AN: 151944 Hom.: 6152 Cov.: 31 AF XY: 0.275 AC XY: 20428 AN XY: 74264

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.0877

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.289

Alfa AF: 0.316 Hom.: 10543

Bravo AF: 0.272

Asia WGS AF: 0.221 AC: 771 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	0.90
DANN	Benign	0.41

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: rs2412522; hg19: chr4-54938543;