rs1759687

chr1-112409197-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CTTNBP2NL	NM_018704.3	c.-133-2997A>G		intron_variant		ENST00000271277.11
CTTNBP2NL	XM_011541781.3	c.-133-2997A>G		intron_variant
CTTNBP2NL	XM_017001806.2	c.-133-2997A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTTNBP2NL	ENST00000271277.11	c.-133-2997A>G		intron_variant		1	NM_018704.3	P1
CTTNBP2NL	ENST00000441739.1	c.-133-2997A>G		intron_variant		3

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

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.0642

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0613

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.0844

Alfa AF: 0.125 Hom.: 213

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
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: rs1759687; hg19: chr1-112951819;