NM_178827.5:c.1234+7730A>G

Variant names:

• chr7-123488966-T-C
• rs7791660
• NM_178827.5:c.1234+7730A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178827.5(IQUB):​c.1234+7730A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,122 control chromosomes in the GnomAD database, including 50,101 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 0.81 (50101 hom., cov: 31)
• Consequence: IQUB NM_178827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 7 publications found

Genes affected

IQUB (HGNC:21995): (IQ motif and ubiquitin domain containing) Predicted to be involved in cilium assembly. Predicted to act upstream of or within smoothened signaling pathway. Predicted to be active in acrosomal vesicle and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178827.5. 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
	IQUB	NM_178827.5	MANE Select	c.1234+7730A>G		intron	N/A	NP_849149.3
	IQUB	NM_001282855.2		c.1234+7730A>G		intron	N/A	NP_001269784.1	Q8NA54-1
	IQUB	NM_001321293.2		c.1234+7730A>G		intron	N/A	NP_001308222.1	Q8NA54-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQUB	ENST00000324698.11	TSL:1 MANE Select	c.1234+7730A>G		intron	N/A	ENSP00000324882.6	Q8NA54-1
	IQUB	ENST00000466202.5	TSL:1	c.1234+7730A>G		intron	N/A	ENSP00000417769.1	Q8NA54-1
	IQUB	ENST00000889595.1		c.1099+7730A>G		intron	N/A	ENSP00000559654.1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123283 AN: 152004 Hom.: 50043 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.811 AC: 123399 AN: 152122 Hom.: 50101 Cov.: 31 AF XY: 0.812 AC XY: 60380 AN XY: 74366

African (AFR) AF: 0.812 AC: 33652 AN: 41468

American (AMR) AF: 0.826 AC: 12627 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2742 AN: 3468

East Asian (EAS) AF: 0.756 AC: 3909 AN: 5174

South Asian (SAS) AF: 0.757 AC: 3654 AN: 4826

European-Finnish (FIN) AF: 0.863 AC: 9142 AN: 10592

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 54982 AN: 67988

Other (OTH) AF: 0.805 AC: 1701 AN: 2114

Alfa AF: 0.807 Hom.: 59327

Bravo AF: 0.810

Asia WGS AF: 0.783 AC: 2721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.52
PhyloP100		-2.6
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

Other links and lift over

dbSNP: rs7791660; hg19: chr7-123129020;