NM_018704.3:c.-133-2997A>G

Variant names:

• chr1-112409197-A-G
• rs1759687
• NM_018704.3:c.-133-2997A>G

Variant summary

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

The NM_018704.3(CTTNBP2NL):​c.-133-2997A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,768 control chromosomes in the GnomAD database, including 1,057 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 0.11 (1057 hom., cov: 31)
• Consequence: CTTNBP2NL NM_018704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 6 publications found

Genes affected

CTTNBP2NL (HGNC:25330): (CTTNBP2 N-terminal like) Enables protein phosphatase 2A binding activity. Acts upstream of or within negative regulation of transmembrane transport; negative regulation of transporter activity; and protein dephosphorylation. Located in actin cytoskeleton. [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 (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTTNBP2NL	NM_018704.3	c.-133-2997A>G		intron_variant	Intron 1 of 5	ENST00000271277.11	NP_061174.1
CTTNBP2NL	XM_011541781.3	c.-133-2997A>G		intron_variant	Intron 1 of 5		XP_011540083.1
CTTNBP2NL	XM_017001806.2	c.-133-2997A>G		intron_variant	Intron 1 of 5		XP_016857295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTTNBP2NL	ENST00000271277.11	c.-133-2997A>G		intron_variant	Intron 1 of 5	1	NM_018704.3	ENSP00000271277.6
CTTNBP2NL	ENST00000441739.1	c.-133-2997A>G		intron_variant	Intron 1 of 5	3		ENSP00000390976.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16337 AN: 151664 Hom.: 1057 Cov.: 31

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.108 AC: 16328 AN: 151768 Hom.: 1057 Cov.: 31 AF XY: 0.104 AC XY: 7697 AN XY: 74144

African (AFR) AF: 0.0706 AC: 2926 AN: 41432

American (AMR) AF: 0.0642 AC: 979 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5168

South Asian (SAS) AF: 0.0613 AC: 294 AN: 4798

European-Finnish (FIN) AF: 0.138 AC: 1441 AN: 10412

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.147 AC: 9973 AN: 67948

Other (OTH) AF: 0.0844 AC: 178 AN: 2110

Alfa AF: 0.124 Hom.: 215

Bravo AF: 0.0988

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.37
PhyloP100		0.34
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: rs1759687; hg19: chr1-112951819;