7-155312071-G-T

Variant names:

• chr7-155312071-G-T
• rs13223383
• XR_007060611.1:n.1266C>A

Variant summary

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

The XR_007060611.1(LOC105375592):​n.1266C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,132 control chromosomes in the GnomAD database, including 36,582 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 0.69 (36582 hom., cov: 33)
• Consequence: LOC105375592 XR_007060611.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 14 publications found

Genes affected

LOC105375592 (HGNC:):

INSIG1 (HGNC:6083): (insulin induced gene 1) This gene encodes an endoplasmic reticulum membrane protein that regulates cholesterol metabolism, lipogenesis, and glucose homeostasis. The encoded protein has six transmembrane helices which contain an effector protein binding site. It binds the sterol-sensing domains of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and is essential for the sterol-mediated trafficking of these two proteins. It promotes the endoplasmic reticulum retention of SCAP and the ubiquitin-mediated degradation of HMG-CoA reductase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000885533.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSIG1	ENST00000885533.1		c.*3801G>T		downstream_gene	N/A	ENSP00000555592.1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104535 AN: 152014 Hom.: 36540 Cov.: 33

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.688 AC: 104626 AN: 152132 Hom.: 36582 Cov.: 33 AF XY: 0.681 AC XY: 50618 AN XY: 74350

African (AFR) AF: 0.726 AC: 30107 AN: 41498

American (AMR) AF: 0.689 AC: 10531 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2100 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1615 AN: 5168

South Asian (SAS) AF: 0.503 AC: 2423 AN: 4818

European-Finnish (FIN) AF: 0.657 AC: 6949 AN: 10576

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48479 AN: 68002

Other (OTH) AF: 0.687 AC: 1453 AN: 2114

Alfa AF: 0.699 Hom.: 123609

Bravo AF: 0.694

Asia WGS AF: 0.480 AC: 1667 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.50
PhyloP100		-0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13223383; hg19: chr7-155103781;