chr1-169376813-C-G

Variant names:

• chr1-169376813-C-G
• rs143882259
• NM_001320973.2:c.302C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001320973.2(BLZF1):​c.302C>G​(p.Ser101Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00182 in 1,613,348 control chromosomes in the GnomAD database, including 4 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S101Y) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (3 hom.)
• Consequence: BLZF1 NM_001320973.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.18
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015164405).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLZF1	NM_001320973.2	MANE Select	c.302C>G	p.Ser101Cys	missense	Exon 3 of 7	NP_001307902.1	Q9H2G9-1
	BLZF1	NM_003666.4		c.302C>G	p.Ser101Cys	missense	Exon 3 of 8	NP_003657.1	Q9H2G9-1
	BLZF1	NM_001320972.2		c.302C>G	p.Ser101Cys	missense	Exon 3 of 3	NP_001307901.1	Q9H2G9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLZF1	ENST00000367808.8	TSL:1 MANE Select	c.302C>G	p.Ser101Cys	missense	Exon 3 of 7	ENSP00000356782.3	Q9H2G9-1
	BLZF1	ENST00000329281.6	TSL:1	c.302C>G	p.Ser101Cys	missense	Exon 3 of 8	ENSP00000327541.2	Q9H2G9-1
	BLZF1	ENST00000367807.7	TSL:1	c.302C>G	p.Ser101Cys	missense	Exon 3 of 3	ENSP00000356781.3	Q9H2G9-2

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 152018 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00116 AC: 290 AN: 250468 AF XY: 0.00109

Gnomad AFR exome AF: 0.000375

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000927

Gnomad NFE exome AF: 0.00213

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00188 AC: 2753 AN: 1461212 Hom.: 3 Cov.: 31 AF XY: 0.00184 AC XY: 1335 AN XY: 726910

African (AFR) AF: 0.000389 AC: 13 AN: 33454

American (AMR) AF: 0.000358 AC: 16 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86230

European-Finnish (FIN) AF: 0.000956 AC: 51 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00232 AC: 2583 AN: 1111592

Other (OTH) AF: 0.00147 AC: 89 AN: 60374

GnomAD4 genome AF: 0.00124 AC: 188 AN: 152136 Hom.: 1 Cov.: 32 AF XY: 0.000968 AC XY: 72 AN XY: 74392

African (AFR) AF: 0.000289 AC: 12 AN: 41522

American (AMR) AF: 0.000656 AC: 10 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00215 AC: 146 AN: 67960

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.0000524 Hom.: 0

Bravo AF: 0.00112

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00130 AC: 5

ExAC AF: 0.00131 AC: 159

EpiCase AF: 0.00186

EpiControl AF: 0.00119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.2
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.098
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.34
MVP		0.48
MPC		0.43
ClinPred		0.039	T
GERP RS		5.1
Varity_R		0.15
gMVP		0.18
Mutation Taster		=76/24	polymorphism

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: rs143882259; hg19: chr1-169346051;