rs1991923

Variant names:

• chr11-85658154-C-T
• rs1991923
• NM_001039618.4:c.*5657G>A

Variant summary

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

The NM_001039618.4(CREBZF):​c.*5657G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 151,776 control chromosomes in the GnomAD database, including 1,462 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 0.13 (1462 hom., cov: 33)
• Consequence: CREBZF NM_001039618.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 5 publications found

Genes affected

CREBZF (HGNC:24905): (CREB/ATF bZIP transcription factor) Enables identical protein binding activity. Involved in negative regulation of gene expression, epigenetic; regulation of transcription, DNA-templated; and response to virus. Located in mitochondrion and nucleoplasm. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREBZF	NM_001039618.4	c.*5657G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000527447.2	NP_001034707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREBZF	ENST00000527447.2	c.*5657G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_001039618.4	ENSP00000433459.1
CREBZF	ENST00000682836.1	n.*2690G>A		non_coding_transcript_exon_variant	Exon 5 of 5			ENSP00000507358.1
CREBZF	ENST00000850607.1	c.*5657G>A		3_prime_UTR_variant	Exon 1 of 1			ENSP00000520895.1
CREBZF	ENST00000682836.1	n.*2690G>A		3_prime_UTR_variant	Exon 5 of 5			ENSP00000507358.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19035 AN: 151660 Hom.: 1451 Cov.: 33

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.126 AC: 19062 AN: 151776 Hom.: 1462 Cov.: 33 AF XY: 0.132 AC XY: 9805 AN XY: 74196

African (AFR) AF: 0.0891 AC: 3695 AN: 41474

American (AMR) AF: 0.197 AC: 3001 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3462

East Asian (EAS) AF: 0.286 AC: 1475 AN: 5166

South Asian (SAS) AF: 0.274 AC: 1324 AN: 4824

European-Finnish (FIN) AF: 0.148 AC: 1561 AN: 10540

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.106 AC: 7187 AN: 67750

Other (OTH) AF: 0.136 AC: 287 AN: 2108

Alfa AF: 0.123 Hom.: 1512

Bravo AF: 0.130

Asia WGS AF: 0.288 AC: 996 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.53
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs1991923; hg19: chr11-85369198;