1-112449240-G-A

Variant names:

• chr1-112449240-G-A
• rs3818729
• NM_018704.3:c.330+68G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018704.3(CTTNBP2NL):​c.330+68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 741,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CTTNBP2NL NM_018704.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018704.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTTNBP2NL	NM_018704.3	MANE Select	c.330+68G>A		intron	N/A	NP_061174.1	Q9P2B4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTTNBP2NL	ENST00000271277.11	TSL:1 MANE Select	c.330+68G>A		intron	N/A	ENSP00000271277.6	Q9P2B4
	CTTNBP2NL	ENST00000862867.1		c.330+68G>A		intron	N/A	ENSP00000532926.1
	CTTNBP2NL	ENST00000862868.1		c.330+68G>A		intron	N/A	ENSP00000532927.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.0000121 AC: 9 AN: 741226 Hom.: 0 AF XY: 0.0000238 AC XY: 9 AN XY: 378274

African (AFR) AF: 0.00 AC: 0 AN: 18700

American (AMR) AF: 0.00 AC: 0 AN: 25320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17120

East Asian (EAS) AF: 0.00 AC: 0 AN: 33242

South Asian (SAS) AF: 0.000167 AC: 9 AN: 53788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3194

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 508236

Other (OTH) AF: 0.00 AC: 0 AN: 35744

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.73
PhyloP100		0.33

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: rs3818729; hg19: chr1-112991862;