7-117711772-G-A

Variant names:

• chr7-117711772-G-A
• rs150547726
• NM_033427.3:c.4757C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine
• congenital bilateral absence of vas deferens

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary chronic pancreatitis

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 2657962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 718 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033427.3. 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
	CTTNBP2	NM_033427.3	MANE Select	c.4757C>T	p.Pro1586Leu	missense	Exon 23 of 23	NP_219499.1	Q8WZ74
	CTTNBP2	NM_001363349.1		c.4703C>T	p.Pro1568Leu	missense	Exon 23 of 23	NP_001350278.1
	CTTNBP2	NM_001363350.1		c.2660C>T	p.Pro887Leu	missense	Exon 23 of 23	NP_001350279.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTTNBP2	ENST00000160373.8	TSL:1 MANE Select	c.4757C>T	p.Pro1586Leu	missense	Exon 23 of 23	ENSP00000160373.3	Q8WZ74
	CTTNBP2	ENST00000446636.5	TSL:5	c.3218C>T	p.Pro1073Leu	missense	Exon 21 of 21	ENSP00000389576.1	H0Y448
	CFTR	ENST00000600166.1	TSL:5	c.367-3986G>A		intron	N/A	ENSP00000470177.1	M0QYZ3

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

GnomAD2 exomes AF: 0.00565 AC: 1400 AN: 247748 AF XY: 0.00568

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 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

African (AFR) AF: 0.000749 AC: 25 AN: 33372

American (AMR) AF: 0.00126 AC: 56 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.000499 AC: 13 AN: 26036

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39638

South Asian (SAS) AF: 0.00166 AC: 143 AN: 85932

European-Finnish (FIN) AF: 0.0235 AC: 1254 AN: 53328

Middle Eastern (MID) AF: 0.00522 AC: 30 AN: 5748

European-Non Finnish (NFE) AF: 0.00550 AC: 6110 AN: 1110092

Other (OTH) AF: 0.00416 AC: 251 AN: 60276

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

African (AFR) AF: 0.00106 AC: 44 AN: 41512

American (AMR) AF: 0.00144 AC: 22 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.0224 AC: 238 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00591 AC: 402 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00528 Hom.: 7

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CTTNBP2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.6
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
Mutation Taster		=90/10	polymorphism

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: rs150547726; hg19: chr7-117351826;