rs10494478

Variant names:

• chr1-169372489-A-G
• rs10494478
• NM_001320973.2:c.28+2939A>G

Variant summary

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

The NM_001320973.2(BLZF1):​c.28+2939A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 152,224 control chromosomes in the GnomAD database, including 729 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 0.084 (729 hom., cov: 32)
• Consequence: BLZF1 NM_001320973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 2 publications found

Genes affected

BLZF1 (HGNC:1065): (basic leucine zipper nuclear factor 1) Enables ubiquitin protein ligase binding activity. Acts upstream of or within Golgi organization and Golgi to plasma membrane protein transport. Located in Golgi apparatus and nucleoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302084 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLZF1	NM_001320973.2	MANE Select	c.28+2939A>G		intron	N/A	NP_001307902.1
	BLZF1	NM_003666.4		c.28+2939A>G		intron	N/A	NP_003657.1
	BLZF1	NM_001320972.2		c.28+2939A>G		intron	N/A	NP_001307901.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLZF1	ENST00000367808.8	TSL:1 MANE Select	c.28+2939A>G		intron	N/A	ENSP00000356782.3
	BLZF1	ENST00000329281.6	TSL:1	c.28+2939A>G		intron	N/A	ENSP00000327541.2
	BLZF1	ENST00000367807.7	TSL:1	c.28+2939A>G		intron	N/A	ENSP00000356781.3

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12822 AN: 152106 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.0842 AC: 12818 AN: 152224 Hom.: 729 Cov.: 32 AF XY: 0.0873 AC XY: 6500 AN XY: 74428

African (AFR) AF: 0.0192 AC: 798 AN: 41564

American (AMR) AF: 0.186 AC: 2846 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3472

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5180

South Asian (SAS) AF: 0.101 AC: 488 AN: 4828

European-Finnish (FIN) AF: 0.0937 AC: 994 AN: 10606

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6886 AN: 67996

Other (OTH) AF: 0.108 AC: 228 AN: 2110

Alfa AF: 0.0928 Hom.: 109

Bravo AF: 0.0868

Asia WGS AF: 0.0580 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.39
PhyloP100		0.12
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: rs10494478; hg19: chr1-169341727;