rs714861

Variant names:

• chr4-54088264-G-A
• rs714861
• ENST00000507166.5:c.1018-186661G>A

Variant summary

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

The ENST00000507166.5(ENSG00000282278):​c.1018-186661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,810 control chromosomes in the GnomAD database, including 14,256 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 0.42 (14256 hom., cov: 31)
• Consequence: ENSG00000282278 ENST00000507166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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]

MORF4L2P1 (HGNC:20403): (mortality factor 4 like 2 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHIC2	XM_047450063.1	c.-1494+3517C>T		intron_variant	Intron 1 of 6		XP_047306019.1
MORF4L2P1		n.54088264G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000282278	ENST00000507166.5	c.1018-186661G>A		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63035 AN: 151692 Hom.: 14218 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.416 AC: 63133 AN: 151810 Hom.: 14256 Cov.: 31 AF XY: 0.407 AC XY: 30226 AN XY: 74182

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.405

Alfa AF: 0.394 Hom.: 1981

Bravo AF: 0.421

Asia WGS AF: 0.290 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.6
DANN	Benign	0.80

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: rs714861; hg19: chr4-54954431; COSMIC: COSV72264526; COSMIC: COSV72264526;