rs4788

Variant names:

• chr12-56712876-A-G
• rs4788
• NM_001365896.1:c.6132T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-56712876-A-G
• chr12-56712876-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001365896.1(NACA):​c.6132T>C​(p.Ile2044Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NACA NM_001365896.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 35 publications found

Genes affected

NACA (HGNC:7629): (nascent polypeptide associated complex subunit alpha) This gene encodes a protein that associates with basic transcription factor 3 (BTF3) to form the nascent polypeptide-associated complex (NAC). This complex binds to nascent proteins that lack a signal peptide motif as they emerge from the ribosome, blocking interaction with the signal recognition particle (SRP) and preventing mistranslocation to the endoplasmic reticulum. This protein is an IgE autoantigen in atopic dermatitis patients. Alternative splicing results in multiple transcript variants, but the full length nature of some of these variants, including those encoding very large proteins, has not been determined. There are multiple pseudogenes of this gene on different chromosomes. [provided by RefSeq, Feb 2016]

ENSG00000306812 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365896.1. 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
	NACA	NM_001365896.1	MANE Select	c.6132T>C	p.Ile2044Ile	synonymous	Exon 8 of 9	NP_001352825.1	E9PAV3-1
	NACA	NM_001113203.3		c.2673T>C	p.Ile891Ile	synonymous	Exon 10 of 11	NP_001106674.2	E9PAV3-2
	NACA	NM_001320194.2		c.543T>C	p.Ile181Ile	synonymous	Exon 7 of 7	NP_001307123.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NACA	ENST00000454682.6	TSL:5 MANE Select	c.6132T>C	p.Ile2044Ile	synonymous	Exon 8 of 9	ENSP00000403817.1	E9PAV3-1
	NACA	ENST00000356769.7	TSL:1	c.543T>C	p.Ile181Ile	synonymous	Exon 7 of 8	ENSP00000349212.3	Q13765-1
	NACA	ENST00000393891.8	TSL:1	c.543T>C	p.Ile181Ile	synonymous	Exon 7 of 8	ENSP00000377469.4	Q13765-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.3
DANN	Benign	0.74
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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

Other links and lift over

dbSNP: rs4788; hg19: chr12-57106660;