rs2412522

Variant names:

• chr4-54072376-A-G
• rs2412522
• ENST00000507166.5:c.1018-202549A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

CHIC2 Gene-Disease associations (from GenCC):

• acute myeloid leukemia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ENSG00000287534 (HGNC:58788):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000507166.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-202549A>G		intron	N/A	ENSP00000423325.1	A0A0B4J203
	ENSG00000287534	ENST00000654316.1		n.1611-4864A>G		intron	N/A
	ENSG00000298834	ENST00000758259.1		n.127-5569T>C		intron	N/A

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

African (AFR) AF: 0.253 AC: 10474 AN: 41444

American (AMR) AF: 0.236 AC: 3599 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3470

East Asian (EAS) AF: 0.0877 AC: 454 AN: 5176

South Asian (SAS) AF: 0.335 AC: 1610 AN: 4802

European-Finnish (FIN) AF: 0.260 AC: 2740 AN: 10540

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21759 AN: 67948

Other (OTH) AF: 0.289 AC: 609 AN: 2108

Alfa AF: 0.312 Hom.: 12989

Bravo AF: 0.272

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.41
PhyloP100		-0.083
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2412522;

hg19: chr4-54938543;