rs1975760

Variant names:

• chr3-125311537-T-C
• rs1975760
• NM_021964.3:c.333+1771A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

DUTP1 (HGNC:31956): (deoxyuridine triphosphatase pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021964.3. 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
	ZNF148	NM_021964.3	MANE Select	c.333+1771A>G		intron	N/A	NP_068799.2
	ZNF148	NM_001348424.1		c.333+1771A>G		intron	N/A	NP_001335353.1
	ZNF148	NM_001348425.2		c.333+1771A>G		intron	N/A	NP_001335354.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF148	ENST00000360647.9	TSL:1 MANE Select	c.333+1771A>G		intron	N/A	ENSP00000353863.4
	ZNF148	ENST00000484491.5	TSL:1	c.333+1771A>G		intron	N/A	ENSP00000420335.1
	ZNF148	ENST00000485866.5	TSL:1	c.333+1771A>G		intron	N/A	ENSP00000420448.1

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

African (AFR) AF: 0.850 AC: 35275 AN: 41494

American (AMR) AF: 0.689 AC: 10521 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2868 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2600 AN: 5166

South Asian (SAS) AF: 0.666 AC: 3205 AN: 4814

European-Finnish (FIN) AF: 0.771 AC: 8134 AN: 10550

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51911 AN: 67990

Other (OTH) AF: 0.782 AC: 1652 AN: 2112

Alfa AF: 0.763 Hom.: 52038

Bravo AF: 0.764

Asia WGS AF: 0.626 AC: 2167 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1975760; hg19: chr3-125030381;