rs3795821

Positions:

• chr1-112457943-A-G
• chr1-112457943-A-T

Variant summary

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

The NM_018704.3(CTTNBP2NL):​c.*531A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 153,842 control chromosomes in the GnomAD database, including 4,110 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 0.21 (4069 hom., cov: 32)
  • Exomes 𝑓: 0.19 (41 hom.)
• Consequence: CTTNBP2NL NM_018704.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTTNBP2NL	NM_018704.3	c.*531A>G		3_prime_UTR_variant	6/6	ENST00000271277.11
CTTNBP2NL	XM_011541781.3	c.*531A>G		3_prime_UTR_variant	6/6
CTTNBP2NL	XM_017001806.2	c.*531A>G		3_prime_UTR_variant	6/6
CTTNBP2NL	XM_047425362.1	c.*531A>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTTNBP2NL	ENST00000271277.11	c.*531A>G		3_prime_UTR_variant	6/6	1	NM_018704.3	P1
CTTNBP2NL	ENST00000607039.1	n.557+569A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31732 AN: 152036 Hom.: 4069 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.194 AC: 327 AN: 1688 Hom.: 41 Cov.: 0 AF XY: 0.199 AC XY: 188 AN XY: 946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.0769

GnomAD4 genome AF: 0.209 AC: 31735 AN: 152154 Hom.: 4069 Cov.: 32 AF XY: 0.218 AC XY: 16206 AN XY: 74370

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.223

Alfa AF: 0.206 Hom.: 2871

Bravo AF: 0.212

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.9
DANN	Benign	0.78

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: rs3795821; hg19: chr1-113000565;