rs1975760

Positions:

• chr3-125311537-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021964.3(ZNF148):​c.333+1771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,078 control chromosomes in the GnomAD database, including 45,665 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 0.77 (45665 hom., cov: 31)
• Consequence: ZNF148 NM_021964.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738

Genes affected

ZNF148 (HGNC:12933): (zinc finger protein 148) The protein encoded by this gene is a member of the Kruppel family of zinc finger DNA binding proteins. The encoded protein activates transcription of the T-cell receptor and intestinal alkaline phosphatase genes but represses transcription of the ornithine decarboxylase, vimentin, gastrin, stomelysin, and enolase genes. Increased expression of this gene results in decreased patient survival rates from colorectal cancer, while mutations in this gene have been associated with global developmental delay, hypoplastic corpus callosum, and dysmorphic facies. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF148	NM_021964.3	c.333+1771A>G		intron_variant		ENST00000360647.9	NP_068799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF148	ENST00000360647.9	c.333+1771A>G		intron_variant		1	NM_021964.3	ENSP00000353863	P1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117069 AN: 151960 Hom.: 45639 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.770 AC: 117149 AN: 152078 Hom.: 45665 Cov.: 31 AF XY: 0.766 AC XY: 56961 AN XY: 74320

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.782

Alfa AF: 0.761 Hom.: 43804

Bravo AF: 0.764

Asia WGS AF: 0.626 AC: 2167 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1975760; hg19: chr3-125030381;