7-123458331-A-T

Variant names:

• chr7-123458331-A-T
• rs940795
• NM_178827.5:c.2008-765T>A

Variant summary

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

The NM_178827.5(IQUB):​c.2008-765T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 151,830 control chromosomes in the GnomAD database, including 50,732 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 0.82 (50732 hom., cov: 32)
• Consequence: IQUB NM_178827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• Publications: 0 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]

ENSG00000232524 (HGNC:):

RNU6-296P (HGNC:47259): (RNA, U6 small nuclear 296, pseudogene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQUB	NM_178827.5	c.2008-765T>A		intron_variant	Intron 11 of 12	ENST00000324698.11	NP_849149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQUB	ENST00000324698.11	c.2008-765T>A		intron_variant	Intron 11 of 12	1	NM_178827.5	ENSP00000324882.6

Frequencies

GnomAD3 genomes AF: 0.817 AC: 123956 AN: 151712 Hom.: 50681 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.817 AC: 124066 AN: 151830 Hom.: 50732 Cov.: 32 AF XY: 0.818 AC XY: 60695 AN XY: 74224

African (AFR) AF: 0.829 AC: 34362 AN: 41444

American (AMR) AF: 0.828 AC: 12601 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2740 AN: 3468

East Asian (EAS) AF: 0.774 AC: 3987 AN: 5154

South Asian (SAS) AF: 0.769 AC: 3705 AN: 4818

European-Finnish (FIN) AF: 0.863 AC: 9102 AN: 10548

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54871 AN: 67872

Other (OTH) AF: 0.812 AC: 1707 AN: 2102

Alfa AF: 0.811 Hom.: 5845

Bravo AF: 0.817

Asia WGS AF: 0.801 AC: 2774 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.48
PhyloP100		0.58
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: rs940795; hg19: chr7-123098385;