rs10249419

chr7-117741752-A-T

Variant summary

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

The NM_033427.3(CTTNBP2):c.3535+4079T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,058 control chromosomes in the GnomAD database, including 19,013 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 0.44 (19013 hom., cov: 32)
• Consequence: CTTNBP2 NM_033427.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

Genes affected

CTTNBP2 (HGNC:15679): (cortactin binding protein 2) This gene encodes a protein with six ankyrin repeats and several proline-rich regions. A similar gene in rat interacts with a central regulator of the actin cytoskeleton. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTTNBP2	NM_033427.3	c.3535+4079T>A		intron_variant		ENST00000160373.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTTNBP2	ENST00000160373.8	c.3535+4079T>A		intron_variant		1	NM_033427.3	P1
CTTNBP2	ENST00000435233.5	c.489+4079T>A		intron_variant		4
CTTNBP2	ENST00000446636.5	c.1997+4079T>A		intron_variant		5
CTTNBP2	ENST00000441556.5	c.*1449+4079T>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66848 AN: 151940 Hom.: 18968 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.440 AC: 66939 AN: 152058 Hom.: 19013 Cov.: 32 AF XY: 0.437 AC XY: 32474 AN XY: 74346

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.0160

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.408

Alfa AF: 0.404 Hom.: 1861

Bravo AF: 0.445

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.50

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: rs10249419; hg19: chr7-117381806;