7-117711772-G-A

Position:

• chr7-117711772-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033427.3(CTTNBP2):​c.4757C>T​(p.Pro1586Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00534 in 1,611,120 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (45 hom.)
• Consequence: CTTNBP2 NM_033427.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.56

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]

CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

CFTR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056162477).
• BP6: Variant 7-117711772-G-A is Benign according to our data. Variant chr7-117711772-G-A is described in ClinVar as [Benign]. Clinvar id is 2657962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTTNBP2	NM_033427.3	c.4757C>T	p.Pro1586Leu	missense_variant	23/23	ENST00000160373.8	NP_219499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTTNBP2	ENST00000160373.8	c.4757C>T	p.Pro1586Leu	missense_variant	23/23	1	NM_033427.3	ENSP00000160373.3

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 718 AN: 152082 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00565 AC: 1400 AN: 247748 Hom.: 10 AF XY: 0.00568 AC XY: 761 AN XY: 134074

Gnomad AFR exome AF: 0.000803

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00172

Gnomad FIN exome AF: 0.0243

Gnomad NFE exome AF: 0.00667

Gnomad OTH exome AF: 0.00413

GnomAD4 exome AF: 0.00540 AC: 7883 AN: 1458920 Hom.: 45 Cov.: 31 AF XY: 0.00533 AC XY: 3865 AN XY: 725362

Gnomad4 AFR exome AF: 0.000749

Gnomad4 AMR exome AF: 0.00126

Gnomad4 ASJ exome AF: 0.000499

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00166

Gnomad4 FIN exome AF: 0.0235

Gnomad4 NFE exome AF: 0.00550

Gnomad4 OTH exome AF: 0.00416

GnomAD4 genome AF: 0.00472 AC: 718 AN: 152200 Hom.: 7 Cov.: 32 AF XY: 0.00518 AC XY: 385 AN XY: 74396

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.00591

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00537 Hom.: 3

Bravo AF: 0.00283

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00523 AC: 45

ExAC AF: 0.00538 AC: 653

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00509

EpiControl AF: 0.00486

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

CTTNBP2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 01, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

CTTNBP2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0056	T
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.26
MVP		0.89
MPC		0.49
ClinPred		0.025	T
GERP RS		5.9
Varity_R		0.10
gMVP		0.24

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: rs150547726; hg19: chr7-117351826;